Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related t...Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.展开更多
BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To invest...BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.展开更多
Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The...Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The randomized controlled trials of Xuebijing injection combined with conventional treatment(experimental group)versus conventional treatment(control group)for sepsis were collected by computer search of Chinese CNKI database,WANFANG database,and VIP database.Literature screening was performed according to the inclusion and exclusion criteria.According to the Cochrane International Collaboration Evaluator Workbook procedure,the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis.Revman 5.3 software was used for systematic meta-analysis.Results:A total of 15 clinical randomized controlled trials with a total of 930 patients were included.Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95%CI(0.38,0.71),P<0.0001],APACHEⅡintegral[WMD=-2.65,95%CI(-3.23,-2.08),P<0.00001];be effective in decreasing D-dimer[WMD=-0.79,95%CI(-1.17,-0.40),P<0.0001],TNF-α[WMD=-36.71,95%CI(-43.04,-30.39),P<0.00001],vWF[WMD=-15.94,95%CI(-27.60,-4.28),P=0.007],sE-selectin[WMD=-118.30,95%CI(-139.65,-96.95),P<0.00001],ESM-1[WMD=-135.44,95%CI(-186.30,-84.57),P<0.00001],sTM[WMD=-56.46,95%CI(-66.39,-46.53),P<0.00001];can effectively increase platelets[WMD=30.78,95%CI(25.65,35.92),P<0.00001].Conclusion:Xuebijing injection can not only effectively reduce the release of inflammatory factors,thereby improving vascular endothelial injury,reducing coagulation disorders and blocking coagulation-inflammation network;it can also increase the level of platelets,thereby repairing injured vascular endothelial cells,which has a certain value to reduce the condition of sepsis and improve the prognosis.It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia.展开更多
Objective:To investigate the therapeutic potential of octaarginine(R8)-modified essential oil from Fructus Alpiniae zerumbet(EOFAZ)lipid microspheres(EOFAZ@^(R8)LM)for cardiovascular therapy.Methods:EOFAZ@^(R8)LM was ...Objective:To investigate the therapeutic potential of octaarginine(R8)-modified essential oil from Fructus Alpiniae zerumbet(EOFAZ)lipid microspheres(EOFAZ@^(R8)LM)for cardiovascular therapy.Methods:EOFAZ@^(R8)LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM,followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury.The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential(MMP),intracellular reactive oxygen species(ROS)levels,as well as inflammatory factors interleukin-6(IL-6)and interleukin-1β(IL-1β)levels.Results:EOFAZ@^(R8)LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells,thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels.Moreover,it attenuated the expression levels of IL-6 and IL-1β,exerting protective effects on the vascular endothelium.Conclusion:Our findings highlight the significant therapeutic potential of EOFAZ@^(R8)LM in cardiovascular therapy,providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.展开更多
Objective Endothelial dysfunction is a central contributor to the vascular complications observed in individuals with diabetes.cAMP response element-binding protein(CREB)plays a crucial role in mediating hyperglycemia...Objective Endothelial dysfunction is a central contributor to the vascular complications observed in individuals with diabetes.cAMP response element-binding protein(CREB)plays a crucial role in mediating hyperglycemia-induced endothelial dysfunction.Phosphatase and tensin homolog(PTEN)has been implicated in the regulation of endothelial inflammation,yet the precise mechanism by which CREB modulates PTEN to protect endothelial cells under high glucose conditions remains unknown.This study aims to elucidate this potential mechanism.Methods Human umbilical vein endothelial cells(HUVECs)were exposed to high glucose(30 mM)or normal glucose(5.5 mM)for 6 days.Cell viability and apoptosis were assessed via the Cell Counting Kit-8 and flow cytometry.To evaluate oxidative stress,the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH),and malondialdehyde(MDA)were measured via commercial assay kits.The interaction between CREB and endothelial specific molecule 1(ESE-1)was assessed via coimmunoprecipitation.Chromatin immunoprecipitation and luciferase reporter assays were used to investigate the transcriptional regulation of PTEN by ESE-1 and CREB.Western blotting was performed to analyze the expression of intercellular adhesion molecule-1 and E-selectin.The adhesion of HUVECs was evaluated via monocyte‒endothelial cell adhesion assays.Results Our findings revealed a direct interaction between CREB and ESE-1,which together regulate PTEN expression to activate the phosphoinositide 3-kinase/protein kinase B pathway.Under high-glucose conditions,we observed significant increases in oxidative stress,inflammatory responses,and adhesion in HUVECs.ESE-1 knockdown reversed these effects,restoring endothelial cell function.Moreover,the overexpression of PTEN in high glucose–treated HUVECs rescued the endothelial injury induced by ESE-1 knockdown,suggesting that PTEN plays a pivotal role in mediating the protective effects.Conclusion ESE-1,through the regulation of CREB-mediated PTEN expression,activates the PI3K/AKT pathway and modulates key processes such as oxidative stress,inflammation,and adhesion in endothelial cells under high-glucose stress.展开更多
Objective To observe the prevention of Fangshuan Capsule(FC)on percutaneous coronary intervention(PCI)induced myocardial damage and vascular endothelial injury in patients with unstable angina pectoris(UAP).Methods To...Objective To observe the prevention of Fangshuan Capsule(FC)on percutaneous coronary intervention(PCI)induced myocardial damage and vascular endothelial injury in patients with unstable angina pectoris(UAP).Methods Totally 100 UAP patients undergoing PCI were assigned to the control group and the展开更多
BACKGROUND:Current studies on CD62 P have focused mainly on cardiovascular diseases,while only few studies have evaluated the effects of CD62 P on the development of sepsis and the association between endothelial cell...BACKGROUND:Current studies on CD62 P have focused mainly on cardiovascular diseases,while only few studies have evaluated the effects of CD62 P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation.This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P(s-CD62P) in plasma and its mechanism in patients with sepsis,thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62 P.METHODS:A total of 70 critically ill patients with systemic inflammatory response syndrome(SIRS) admitted to intensive care unit(ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to the diagnostic criteria of sepsis/SIRS,the patients were divided into two groups:a sepsis group(n=38) and a SIRS group(n=32).Another 20 healthy volunteers served as a control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of the patients including age,sex,body mass index(BMI),smoking and alcohol addict were compared among the groups.Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay(ELISA) to detect the plasma levels of S-CD62 P,TNF-α,and hs-CRP.And variables of coagulation function such as platelet(PLT),prothrombin(PT),activated partial thromboplastin time(APTT),D-dimer and antithrombin-Ⅲ(AT-Ⅲ) were analyzed during 24 hours after admission to ICU.Meanwhile sequential organ failure assessment(SOFA) score of critically ill patients was evaluated.Data were expressed as meanistandard deviation and were statistically analyzed by using SPSS 17.0statistical software.The differences in plasma levels of S-CD62 P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test.The relations between S-CD62 P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis.Changes were considered as statistically significant if P value was less than 0.05.RESULTS:Compared with the control group and SIRS group,the sepsis group demonstrated significantly higher levels of S-CD62 P,TNF-a and highly sensitive C-reactive protein(hs-CRP)(PO.05).The plasma levels of D-dimer,PT,and APTT in the sepsis and SIRS groups were significantly higher than those in the control group,while the platelet count and the activity of AT-Ⅲ were obviously lower(P<0.05).In the sepsis group,the plasma levels of hs-CRP and TNF-a were positively correlated with PT,APTT,and D-dimer,and negatively correlated with AT-Ⅲ and PLT(P<0.05).The plasma levels of S-CD62 P were significantly correlated with the plasma levels of TNF-a,hs-CRP,D-dimer,PT,and APTT,whereas they were correlated negatively well with PLT and AT-Ⅲ(P<0.05).CONCLUSIONS:The concentration of plasma S-CD62 P is elevated as a early biomarker in patients with sepsis,and it serves as one of the pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promote each other,aggravating the severity of sepsis.Plasma S-CD62 P may be an important factor for the development of coagulation and inflammatory reaction.展开更多
BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on in...BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE： To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN： A randomized controlled animal tria SETTNG： Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS： Sixty-five healthy male New Zealand rabbits of clean degree, weighing （2.6±0.2） kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia （Beijing Zhongshan Company）, recombinant VEGF165 （Peprotech Company, USA）, biotinylated second antibody and ABC compound （Wuhan Boster Company） were applied. METHODS： The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. （1） The rabbits were randomly divided into three groups： sham-operated group （n=15）, control group （n=25） and VEGF-treated group （n=-25）. In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion （MCAO） induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 （2.5 mg/L） was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. （2） The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES： The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS： All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group： There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [（6.0±1.1）, （9.0±0.9） microvessels; （3.0±1.1）, （3.0±1.1） microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [（8.3±2.0）, （13.4±1.4）, （15.5±2.3）, （6.8± 1.0） microvessels; （3.4±0.6）, （6.0±1.1）, （9.0±0.9）, （3.2±0.8） microvessels; P 〈 0.01]. （2） Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites： There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION： Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.展开更多
Objective: To observe the changes of plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin in children undergoing cardiac procedure and to st...Objective: To observe the changes of plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin in children undergoing cardiac procedure and to study the effects of cardiopulmonary bypass (CPB) on the injury or activation of endothelial cells and vascular permeability. Methods: Twenty children undergoing cardiac operation with CPB were selected in the study. Plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin were measured after anesthetic induction (baseline), bypass for 20 minutes, at the end of CPB, and at 2, 4, and 18 h after the end of CPB. Results: The plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, and urinary microalbumin began to increase at 2 h after the end of CPB, and remained higher than that of the baseline, while the concentration of tumor necrosis factor α increased only at the end CPB and at 2 h after the end of CPB. Conclusion: Cardiopulmonary bypass can induce inflammatory response, resulting in the activation or injury of vascular endothelial cells, and can increase the vascular permeability.展开更多
Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosc...Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.展开更多
AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METH...AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed.RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement.CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.展开更多
Objective:To analyze the mechanism of HSP70 regulating endothelial cell injury in patients with acute sepsis.Methods:From February 2017 to December 2018,3 patients with acute sepsis in our hospital were selected as th...Objective:To analyze the mechanism of HSP70 regulating endothelial cell injury in patients with acute sepsis.Methods:From February 2017 to December 2018,3 patients with acute sepsis in our hospital were selected as the observation group,and 3 patients with fracture undergoing surgical treatment were selected as the control group.The endothelial cells were extracted and divided into blank subgroup,10 mg/L,50 mg/L and 100 mg/L subgroups.The cell viability of each group was detected by MTT,the nucleus morphology was observed by fluorescence microscope,and autophagosomes of endothelial cells were observed by transmission electron microscope,and then the level of Bcl-2,Beclin-1 andβ-actin protein expression were detected.Results:HSP70 intervention can effectively improve the endothelial cell vitality of patients with acute sepsis.The cell viability of 100 mg/L subgroup was the highest in the observation group and the control group,and the cell viability of the blank subgroup was the lowest,and the difference was statistically significant(P<0.05).Compared with the control group,the endothelial cell nuclear defect of acute sepsis patients was serious.HSP70 intervention can effectively improve the nuclear morphology,autophagy morphology and structural morphology,and the 100 mg/L subgroup had the best nuclear morphology and autophagy morphology.HSP70 intervention can effectively improve the levels of Bcl-2 and beclin-1 in endothelial cells of patients with acute sepsis.The levels of Bcl-2 and beclin-1 were the highest in the 100 mg/L subgroup of the observation group and the control group,and the lowest in the blank subgroup,and the difference was statistically significant(P<0.05).Conclusion:HSP70 can effectively regulate the level of Bcl-2 in endothelial cells of patients with acute sepsis,which effectively inhibit cell apoptosis and alleviate cell skin damage.展开更多
To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Ca...To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.展开更多
Background It＇s established that Lectin-like involved in intimal hyperplasia after balloon injury oxidized low-density lipoprotein receptor-l（LOX-1） is The recent evidence also suggests that valsartan has an antia...Background It＇s established that Lectin-like involved in intimal hyperplasia after balloon injury oxidized low-density lipoprotein receptor-l（LOX-1） is The recent evidence also suggests that valsartan has an antiatheroscletic effect. In this study, the expression of LOX-1 and the effect of valsartan on its expression was investigated in rat aorta after balloon injury. Methods Rat model of aortic endothelial denudation was induced by 2F balloon catheter. Rats were randomly divided into three groups： control, operationand valsartan treatment. The aortic tissues were taken from rats in each group on days 14 and 28 after surgery. The thickness of vascular wall was measured with HE stain, LOX-1 mRNA and protein were determined by reverse transcription-polymerse chain reaction （RT-PCR） and immunohistochemistry, respectively. Results Compared with the control group, significant intimal thickening was observed at day 14 and 28 after injury. Compared with the operation group, intimal thickness of each time point was significantly decreased in valsartan treatment group. At day 14 and 28 after balloon injury, the expression levels of LOX-1 mRNA and protein were significantly increased, and were greatly decreased after valsartan treatment. Conclusions The expression of LOX-1 is increased after endothelial injury. Valsartan inhibits aortic intimal thickening induced by endothelial denudation, which is associated with the downregulation of LOX-1 expression.展开更多
Coronary no-reflow phenomenon belongs to a type of coronary microcirculation disturbance,and its main pathogenic factors are vascular endothelial cell injury,microembolism and inflammatory reaction,which are correspon...Coronary no-reflow phenomenon belongs to a type of coronary microcirculation disturbance,and its main pathogenic factors are vascular endothelial cell injury,microembolism and inflammatory reaction,which are corresponding to the pathogenesis of choroid injury,blood stasis and heat toxin in traditional Chinese medicine,such as NO,ET-1,chemokine,IL and other cytokines.The degree of improvement of patients'symptoms and laboratory examination data provide a basis for traditional Chinese medicine compound prescription,monomer and traditional Chinese medicine characteristic therapy for the treatment of no-reflow phenomena(NRP).Combined with related factors,the author summarizes the research progress of traditional Chinese medicine treatment of NRP in recent years,in order to provide clinical reference.展开更多
Objective To investigate the effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on limb ischemia/reperfusion injury of rats and the mechanism Methods The hind limb ische...Objective To investigate the effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on limb ischemia/reperfusion injury of rats and the mechanism Methods The hind limb ischemia/reperfusion injury of male SD rats was induced by tourniquet for 2 hours and then reperfusing for 12 hours with administration of different agents Animals were divided into control, bFGF 10 and bFGF 50, VEGF 10 and VEGF 50 group by infusing physiological saline, 10 and 50?μg/kg bFGE, 10 and 50?μg/kg VEGF, respectively Blood was collected to determine malonyldialdehyde (MDA), and the ischemic reperfused gastrocnemius muscle and the contralateral control one were harvested together for measurement of tissue viability, water content, myeloperoxidose (MPO) activity, ATP and MDA concentration Results Compared with control group, tissue viability of ischemia/reperfusion limb in bFGF 10 and bFGF 50 group increased by 16 0% ( P <0 05) and 32 8% ( P <0 01), ATP content increased by 14 8% and 35 6% ( P <0 01), and plasma MDA level decreased by 45 2% and 56 2% ( P <0 01) 10?μg/kg bFGF had no significant effect on tissue water content, MPO activity, MDA concentration of ischemia/reperfusion limb, while 50?μg/kg of bFGF lowered these values by 15 7%, 32 5% and 13 6% ( P <0 05) and 14 7% ( P <0 01), MPO activity augmented by 44 9% and 96 1% ( P <0 01), ATP content decreased by 13 1% ( P <0 05) and 33 3% ( P <0 01) Plasma and tissue MDA concentrations in VEGF 10 group had no significant changes ( P >0 05), while in VEGF 50 group, these values were elevated by 46 4% and 38 6% ( P <0 01) Conclusion bFGF attenuated, while VEGF exacerbated ischemia/reperfusion injury of rat limb significantly, the mechanism of which was probably related to preventing or enhancing lipid peroxide, and increasing or decreasing energy store展开更多
Objective To investigate the expression of endoplasmic reticulum stress(ESR)marker C/EBP homologous protein-10(CHOP-10)in the human aortic endothelial cells(HAEC)under the ischemia and hypoxia stress and to study the ...Objective To investigate the expression of endoplasmic reticulum stress(ESR)marker C/EBP homologous protein-10(CHOP-10)in the human aortic endothelial cells(HAEC)under the ischemia and hypoxia stress and to study the effects of atorvastatin on the process.Methods The cultured HAEC were divided into normal control group,ischemia/hypoxia model group。展开更多
Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This stu...Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.展开更多
Background:Ischemic heart disease is a leading cause of mortality and disability worldwide among cardiovascular conditions.Myocardial ischemia-reperfusion injury(MIRI)occurs following percutaneous coronary interventio...Background:Ischemic heart disease is a leading cause of mortality and disability worldwide among cardiovascular conditions.Myocardial ischemia-reperfusion injury(MIRI)occurs following percutaneous coronary intervention,during which neutrophils generate neutrophil extracellular traps(NETs)in response to injury.This study aims to elucidate the mechanisms underlying NET activation and its impact on MIRI.Methods:Sham and MIRI rat models were established.Various techniques,including enzyme-linked immunosorbent assay,hematoxylin and eosin staining,Masson staining,and transmission electron microscopy,were used to assess endothelial cell injury and myocardial tissue inflammation.Immunofluorescence was employed to evaluate NET activation in tissues,peripheral blood neutrophils,and protein colocalization.MitoTracker and ER-Tracker staining were conducted to assess the formation of mitochondria-associated membranes(MAMs).Extracted NETs were applied to conduct microvascular endothelial cell tube formation assay and flow cytometry.RNA-sequencing and immunoprecipitation-mass spectrometry were applied to determine the key regulators.Flow cytometry and Western blot were used to assess Ca^(2+)and mitophagy levels in neutrophils.Deoxyribonuclease I,NET inhibitor,was injected into MIRI rats to evaluate the in vivo effects of NET modulation on MIRI severity.Results:MIRI was often accompanied by cardiac microvascular endothelial cell(CMEC)injury and inflammation.Lactate mediated H3K18 lactylation at the MICU3 promoter in neutrophils,enhancing its transcription and leading to elevated MICU3 levels.Besides,lactate also promoted the interaction between MICU3 and AASR1,stabilizing MICU3 through lactylation.Up-regulated MICU3 interacted with VDAC1,facilitating MAM formation,excessive Ca^(2+)uptake,mitochondrial dysfunction,mitophagy activation,and NET activation.Elevated NET level exacerbated CMEC dysfunction,further aggravating MIRI.Conclusion:Lactate-driven MICU3 transcriptional activation and stabilization facilitates NET formation,contributing to MIRI development.展开更多
基金supported by the National Natural Science Foundation of China(grant No.81973592)the Shaanxi Provincial Administration of Traditional Chinese Medicine Project(grant No.2021-GJ-JC004).
文摘Background:Heat and Blood Stasis Syndrome(HBSS),a syndrome in traditional Chinese medicine is intrinsically linked to vascular endothelial injury.Taohe Chengqi Decoction(THCQT)is considered to treat diseases related to HBSS by improving inflammatory response,oxidative stress,and blood circulation disorder.This study aimed to elucidate the therapeutic effects and underlying mechanisms of THCQT on vascular endothelial injury induced by HBSS.Methods:LC-MS/MS was used to analyze the chemical components of THCQT.The intervention involved administering saline and appropriate drugs to rats via gavage for 21 days,followed by 24-h repeated tail vein injections of LPS to replicate the HBSS model.Pharmacodynamic assessments included measuring rat body temperature,hemorheology,coagulation function,fever mediators,inflammatory factors,vascular endothelial injury factors,and aortic histopathology to evaluate the preventive effect of THCQT on vascular endothelial injury caused by HBSS.Additionally,proteomics and transcriptomics analyses elucidated THCQT’s impact on mRNA and protein expression levels,further validated by quantitative real-time PCR and Western blot analysis.Results:THCQT was detected to contain 293 chemical components,and some active ingredients with high levels have anti-inflammatory,antioxidant,and inhibiting platelet aggregation properties.Pharmacodynamic results demonstrated that H-THCQT significantly suppressed the elevation of body temperature and downregulated TNF-α,cAMP,and PGE2 expression levels.Additionally,it attenuated the increase in WBV and PV,and prolonged APTT,PT,and TT.It enhanced the expression of NO and PGI2 in plasma,inhibiting ET-1 and TXA2 expression,thus ameliorating aortic pathological injury.Combined transcriptomics and proteomics analyses of the KEGG pathway suggest that the MAPK pathway is crucial in mitigating vascular endothelial injury induced by HBSS through THCQT administration.Furthermore,quantitative real-time PCR and Western blot analyses of the aorta indicated that THCQT inhibits the mRNA and protein phosphorylation levels of p38MAPK,ERK,and JNK in the MAPK signaling pathway of HBSS rats.Conclusion:Our work not only helps explore the common mechanism of THCQT in treating multi-system diseases induced by vascular endothelial injury due to HBSS but also provides a valuable research method for investigating the mechanisms underlying traditional Chinese medicine syndromes.
基金Supported by National Natural Science Foundation of China,No.8187150391 and No.81904126Science and Technology Commission of Shanghai Municipality,No.20Y21901800.
文摘BACKGROUND Endothelial injury and inflammation are the main pathological changes in hyperuricemic nephropathy(HN);however,they have not been assessed in patients in the early,middle,and late phases of HN.AIM To investigate endothelial injury and inflammatory conditions between patients with HN at chronic kidney disease(CKD)stages 3-4 and CKD 1-2.METHODS This study enrolled 80 patients(49 and 31 with HN at CKD stage 1-2 and 3-4,respectively)from the Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine between July 2021 and January 2022.Plasma levels of heparan sulfate,endocan,oxidized low-density lipoprotein(Ox-LDL),E-selectin,soluble intercellular adhesion molecule-1(slCAM1),interleukin(IL)-1β,and IL-6 and urine levels of lipocalin-type prostaglandin D synthase(L-PGDS),IL-1β,and IL-6 were measured using enzyme-linked immunosorbnent assay.RESULTS Comparison between patients with HN at CKD 1-2 and those with HN at CKD 3-4 showed that age and disease course were significant factors(P<0.001 and P<0.010,respectively).There were no statistical differences in sex,heart rate,body mass index,and systolic and diastolic blood pressures.The incidence of hypertension was also significant(P=0.03).Plasma levels of heparin sulfate(P<0.001),endocan(P=0.034),E-selectin(P<0.001),slCAM1(P<0.001),IL-1β(P=0.006),and IL-6(P=0.004)and the urine levels of L-PGDS(P<0.001),IL-1β(P=0.003),and IL-6(P<0.001)were high in patients with HN at CKD 3-4 than in those with HN at CKD 1-2.The difference in plasma Ox-LDL levels was not significant(P=0.078).CONCLUSION Vascular endothelial injury and inflammation were higher in patients with HN at CKD3-4 than at CKD 1-2.Plasma heparin sulfate and slCAM1 levels are synergistic factors for CKD staging in HN.
基金Shaanxi Provincial Administration of Traditional Chinese Medicine 2020 Special Project of Pneumonia Scientific Research on Prevention and Treatment of Novel Coronavirus with Traditional Chinese Medicine(No.SZY-KJCYC-2020-YJ001)Shaanxi Provincial Department of Science and Technology Key Research and Development Project(No.2017ZDXM-SF-109)Shaanxi Provincial Infectious Diseases Clinical Medicine Research Center(Integrated Traditional Chinese and Western Medicine)Project(No.2020LCZX-02)。
文摘Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The randomized controlled trials of Xuebijing injection combined with conventional treatment(experimental group)versus conventional treatment(control group)for sepsis were collected by computer search of Chinese CNKI database,WANFANG database,and VIP database.Literature screening was performed according to the inclusion and exclusion criteria.According to the Cochrane International Collaboration Evaluator Workbook procedure,the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis.Revman 5.3 software was used for systematic meta-analysis.Results:A total of 15 clinical randomized controlled trials with a total of 930 patients were included.Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95%CI(0.38,0.71),P<0.0001],APACHEⅡintegral[WMD=-2.65,95%CI(-3.23,-2.08),P<0.00001];be effective in decreasing D-dimer[WMD=-0.79,95%CI(-1.17,-0.40),P<0.0001],TNF-α[WMD=-36.71,95%CI(-43.04,-30.39),P<0.00001],vWF[WMD=-15.94,95%CI(-27.60,-4.28),P=0.007],sE-selectin[WMD=-118.30,95%CI(-139.65,-96.95),P<0.00001],ESM-1[WMD=-135.44,95%CI(-186.30,-84.57),P<0.00001],sTM[WMD=-56.46,95%CI(-66.39,-46.53),P<0.00001];can effectively increase platelets[WMD=30.78,95%CI(25.65,35.92),P<0.00001].Conclusion:Xuebijing injection can not only effectively reduce the release of inflammatory factors,thereby improving vascular endothelial injury,reducing coagulation disorders and blocking coagulation-inflammation network;it can also increase the level of platelets,thereby repairing injured vascular endothelial cells,which has a certain value to reduce the condition of sepsis and improve the prognosis.It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia.
基金supported by the National Natural Science Foundation of China(Nos.82260827 and U1812403-4-4)the Guizhou Provincial Science Technology Project(No.ZK[2022]380)+3 种基金the Guizhou Provincial Natural Science Foundation(Nos.[2020]1Z069 and[2020]1Y210)the Guizhou Provincial Scientific and Technologic Innovation Base(No.[2023]003)the Cultivation Project of National Natural Science Foundation of Guizhou Medical University(Nos.21NSFCP47 and 20NSP053)the High level Innovation Talents(No.GCC[2023]048)。
文摘Objective:To investigate the therapeutic potential of octaarginine(R8)-modified essential oil from Fructus Alpiniae zerumbet(EOFAZ)lipid microspheres(EOFAZ@^(R8)LM)for cardiovascular therapy.Methods:EOFAZ@^(R8)LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM,followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury.The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential(MMP),intracellular reactive oxygen species(ROS)levels,as well as inflammatory factors interleukin-6(IL-6)and interleukin-1β(IL-1β)levels.Results:EOFAZ@^(R8)LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells,thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels.Moreover,it attenuated the expression levels of IL-6 and IL-1β,exerting protective effects on the vascular endothelium.Conclusion:Our findings highlight the significant therapeutic potential of EOFAZ@^(R8)LM in cardiovascular therapy,providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2020D01C210).
文摘Objective Endothelial dysfunction is a central contributor to the vascular complications observed in individuals with diabetes.cAMP response element-binding protein(CREB)plays a crucial role in mediating hyperglycemia-induced endothelial dysfunction.Phosphatase and tensin homolog(PTEN)has been implicated in the regulation of endothelial inflammation,yet the precise mechanism by which CREB modulates PTEN to protect endothelial cells under high glucose conditions remains unknown.This study aims to elucidate this potential mechanism.Methods Human umbilical vein endothelial cells(HUVECs)were exposed to high glucose(30 mM)or normal glucose(5.5 mM)for 6 days.Cell viability and apoptosis were assessed via the Cell Counting Kit-8 and flow cytometry.To evaluate oxidative stress,the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH),and malondialdehyde(MDA)were measured via commercial assay kits.The interaction between CREB and endothelial specific molecule 1(ESE-1)was assessed via coimmunoprecipitation.Chromatin immunoprecipitation and luciferase reporter assays were used to investigate the transcriptional regulation of PTEN by ESE-1 and CREB.Western blotting was performed to analyze the expression of intercellular adhesion molecule-1 and E-selectin.The adhesion of HUVECs was evaluated via monocyte‒endothelial cell adhesion assays.Results Our findings revealed a direct interaction between CREB and ESE-1,which together regulate PTEN expression to activate the phosphoinositide 3-kinase/protein kinase B pathway.Under high-glucose conditions,we observed significant increases in oxidative stress,inflammatory responses,and adhesion in HUVECs.ESE-1 knockdown reversed these effects,restoring endothelial cell function.Moreover,the overexpression of PTEN in high glucose–treated HUVECs rescued the endothelial injury induced by ESE-1 knockdown,suggesting that PTEN plays a pivotal role in mediating the protective effects.Conclusion ESE-1,through the regulation of CREB-mediated PTEN expression,activates the PI3K/AKT pathway and modulates key processes such as oxidative stress,inflammation,and adhesion in endothelial cells under high-glucose stress.
文摘Objective To observe the prevention of Fangshuan Capsule(FC)on percutaneous coronary intervention(PCI)induced myocardial damage and vascular endothelial injury in patients with unstable angina pectoris(UAP).Methods Totally 100 UAP patients undergoing PCI were assigned to the control group and the
文摘BACKGROUND:Current studies on CD62 P have focused mainly on cardiovascular diseases,while only few studies have evaluated the effects of CD62 P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation.This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P(s-CD62P) in plasma and its mechanism in patients with sepsis,thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62 P.METHODS:A total of 70 critically ill patients with systemic inflammatory response syndrome(SIRS) admitted to intensive care unit(ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to the diagnostic criteria of sepsis/SIRS,the patients were divided into two groups:a sepsis group(n=38) and a SIRS group(n=32).Another 20 healthy volunteers served as a control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of the patients including age,sex,body mass index(BMI),smoking and alcohol addict were compared among the groups.Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay(ELISA) to detect the plasma levels of S-CD62 P,TNF-α,and hs-CRP.And variables of coagulation function such as platelet(PLT),prothrombin(PT),activated partial thromboplastin time(APTT),D-dimer and antithrombin-Ⅲ(AT-Ⅲ) were analyzed during 24 hours after admission to ICU.Meanwhile sequential organ failure assessment(SOFA) score of critically ill patients was evaluated.Data were expressed as meanistandard deviation and were statistically analyzed by using SPSS 17.0statistical software.The differences in plasma levels of S-CD62 P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test.The relations between S-CD62 P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis.Changes were considered as statistically significant if P value was less than 0.05.RESULTS:Compared with the control group and SIRS group,the sepsis group demonstrated significantly higher levels of S-CD62 P,TNF-a and highly sensitive C-reactive protein(hs-CRP)(PO.05).The plasma levels of D-dimer,PT,and APTT in the sepsis and SIRS groups were significantly higher than those in the control group,while the platelet count and the activity of AT-Ⅲ were obviously lower(P<0.05).In the sepsis group,the plasma levels of hs-CRP and TNF-a were positively correlated with PT,APTT,and D-dimer,and negatively correlated with AT-Ⅲ and PLT(P<0.05).The plasma levels of S-CD62 P were significantly correlated with the plasma levels of TNF-a,hs-CRP,D-dimer,PT,and APTT,whereas they were correlated negatively well with PLT and AT-Ⅲ(P<0.05).CONCLUSIONS:The concentration of plasma S-CD62 P is elevated as a early biomarker in patients with sepsis,and it serves as one of the pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promote each other,aggravating the severity of sepsis.Plasma S-CD62 P may be an important factor for the development of coagulation and inflammatory reaction.
文摘BACKGROUND： Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor （VEGF） on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic. OBJECTIVE： To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia /reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia. DESIGN： A randomized controlled animal tria SETTNG： Department of Medical Imaging, Second Hospital of Hebei Medical University MATERIALS： Sixty-five healthy male New Zealand rabbits of clean degree, weighing （2.6±0.2） kg, aged 4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia （Beijing Zhongshan Company）, recombinant VEGF165 （Peprotech Company, USA）, biotinylated second antibody and ABC compound （Wuhan Boster Company） were applied. METHODS： The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy, Second Hospital of Hebei Medical University from May to August in 2005. （1） The rabbits were randomly divided into three groups： sham-operated group （n=15）, control group （n=25） and VEGF-treated group （n=-25）. In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion （MCAO） induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165 （2.5 mg/L） was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabbits in the sham-operated group were only drilled but not administrated. （2） The experimental indexes were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The brain tissues in the surrounding regions of the infarcted sites were collected. The positive expressions of the factors of vascular pseudohemophilia in vascular endothelial cells were analyzed with immunohistochemical method. The microvessels in unit statistical field were counted with the imaging analytical software. MAIN OUTCOME MEASURES： The changes of microvascular density in the brain tissue and the positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of the infarcted sites were observed on the 3^rd 7^th, 14^th, 28^th and 70^th days of the experiment. RESULTS： All the 65 New Zealand rabbits were involved in the analysis of results without deletion. Changes of the number of microvessels at different time points in each group： There were no obvious changes at different time points in the sham-operated group. The numbers of microvessels at 7 and 14 days were obviously more in the control group than in the sham-operated group [（6.0±1.1）, （9.0±0.9） microvessels; （3.0±1.1）, （3.0±1.1） microvessels; P〈 0.05-0.01], and those at 3, 7, 14 and 28 days were obviously more in the VEGF-treated group than in the control group [（8.3±2.0）, （13.4±1.4）, （15.5±2.3）, （6.8± 1.0） microvessels; （3.4±0.6）, （6.0±1.1）, （9.0±0.9）, （3.2±0.8） microvessels; P 〈 0.01]. （2） Positive expressions of the factors of vascular pseudohemophilia in the surrounding regions of infarcted sites： There were no obvious changes at different time points in the sham-operated group. In the control group, the changing law of the expressions was the same as that for the number of microvessels that the expression began to mildly increase at 7 days, reached the peak value at 14 days, and began to reduce at 28 days. In the VEGF-treated group, the expression was obviously increased at 3 days, also reached the peak value at 14 days, and reduced to the normal level at 70 days, but the expressions were obviously stronger than those in the control group at the same time points. CONCLUSION： Angiogenesis can be obviously induced in rabbits after the focal cerebral ischemia/reperfusion injury is treated with VEGF for 18 days.
文摘Objective: To observe the changes of plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin in children undergoing cardiac procedure and to study the effects of cardiopulmonary bypass (CPB) on the injury or activation of endothelial cells and vascular permeability. Methods: Twenty children undergoing cardiac operation with CPB were selected in the study. Plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin were measured after anesthetic induction (baseline), bypass for 20 minutes, at the end of CPB, and at 2, 4, and 18 h after the end of CPB. Results: The plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, and urinary microalbumin began to increase at 2 h after the end of CPB, and remained higher than that of the baseline, while the concentration of tumor necrosis factor α increased only at the end CPB and at 2 h after the end of CPB. Conclusion: Cardiopulmonary bypass can induce inflammatory response, resulting in the activation or injury of vascular endothelial cells, and can increase the vascular permeability.
文摘Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.
文摘AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed.RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement.CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.
基金Talent training plan of Shanghai Pudong New Area public interest hospital(No.GLRq2018-03)Key specialty of health system in Pudong New Area(No.PWZzk2017-05)Youth Science and technology project of health and family planning in Pudong New Area in 2018(No.PW2018B-03)。
文摘Objective:To analyze the mechanism of HSP70 regulating endothelial cell injury in patients with acute sepsis.Methods:From February 2017 to December 2018,3 patients with acute sepsis in our hospital were selected as the observation group,and 3 patients with fracture undergoing surgical treatment were selected as the control group.The endothelial cells were extracted and divided into blank subgroup,10 mg/L,50 mg/L and 100 mg/L subgroups.The cell viability of each group was detected by MTT,the nucleus morphology was observed by fluorescence microscope,and autophagosomes of endothelial cells were observed by transmission electron microscope,and then the level of Bcl-2,Beclin-1 andβ-actin protein expression were detected.Results:HSP70 intervention can effectively improve the endothelial cell vitality of patients with acute sepsis.The cell viability of 100 mg/L subgroup was the highest in the observation group and the control group,and the cell viability of the blank subgroup was the lowest,and the difference was statistically significant(P<0.05).Compared with the control group,the endothelial cell nuclear defect of acute sepsis patients was serious.HSP70 intervention can effectively improve the nuclear morphology,autophagy morphology and structural morphology,and the 100 mg/L subgroup had the best nuclear morphology and autophagy morphology.HSP70 intervention can effectively improve the levels of Bcl-2 and beclin-1 in endothelial cells of patients with acute sepsis.The levels of Bcl-2 and beclin-1 were the highest in the 100 mg/L subgroup of the observation group and the control group,and the lowest in the blank subgroup,and the difference was statistically significant(P<0.05).Conclusion:HSP70 can effectively regulate the level of Bcl-2 in endothelial cells of patients with acute sepsis,which effectively inhibit cell apoptosis and alleviate cell skin damage.
文摘To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.
基金supported by Science and Technology sponsor project of Shandong Province(No.2012G0021851)
文摘Background It＇s established that Lectin-like involved in intimal hyperplasia after balloon injury oxidized low-density lipoprotein receptor-l（LOX-1） is The recent evidence also suggests that valsartan has an antiatheroscletic effect. In this study, the expression of LOX-1 and the effect of valsartan on its expression was investigated in rat aorta after balloon injury. Methods Rat model of aortic endothelial denudation was induced by 2F balloon catheter. Rats were randomly divided into three groups： control, operationand valsartan treatment. The aortic tissues were taken from rats in each group on days 14 and 28 after surgery. The thickness of vascular wall was measured with HE stain, LOX-1 mRNA and protein were determined by reverse transcription-polymerse chain reaction （RT-PCR） and immunohistochemistry, respectively. Results Compared with the control group, significant intimal thickening was observed at day 14 and 28 after injury. Compared with the operation group, intimal thickness of each time point was significantly decreased in valsartan treatment group. At day 14 and 28 after balloon injury, the expression levels of LOX-1 mRNA and protein were significantly increased, and were greatly decreased after valsartan treatment. Conclusions The expression of LOX-1 is increased after endothelial injury. Valsartan inhibits aortic intimal thickening induced by endothelial denudation, which is associated with the downregulation of LOX-1 expression.
基金Shandong traditional Chinese Medicine Science and Technology Development Plan Project(No.2015-075)Shandong traditional Chinese Medicine Science and Technology Development Plan Project(No.2019-0191)+1 种基金Shandong Natural Science Foundation Project(No.ZR2019MH032)Shandong Natural Science Foundation Youth Project(No.ZR2020QH333)。
文摘Coronary no-reflow phenomenon belongs to a type of coronary microcirculation disturbance,and its main pathogenic factors are vascular endothelial cell injury,microembolism and inflammatory reaction,which are corresponding to the pathogenesis of choroid injury,blood stasis and heat toxin in traditional Chinese medicine,such as NO,ET-1,chemokine,IL and other cytokines.The degree of improvement of patients'symptoms and laboratory examination data provide a basis for traditional Chinese medicine compound prescription,monomer and traditional Chinese medicine characteristic therapy for the treatment of no-reflow phenomena(NRP).Combined with related factors,the author summarizes the research progress of traditional Chinese medicine treatment of NRP in recent years,in order to provide clinical reference.
文摘Objective To investigate the effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on limb ischemia/reperfusion injury of rats and the mechanism Methods The hind limb ischemia/reperfusion injury of male SD rats was induced by tourniquet for 2 hours and then reperfusing for 12 hours with administration of different agents Animals were divided into control, bFGF 10 and bFGF 50, VEGF 10 and VEGF 50 group by infusing physiological saline, 10 and 50?μg/kg bFGE, 10 and 50?μg/kg VEGF, respectively Blood was collected to determine malonyldialdehyde (MDA), and the ischemic reperfused gastrocnemius muscle and the contralateral control one were harvested together for measurement of tissue viability, water content, myeloperoxidose (MPO) activity, ATP and MDA concentration Results Compared with control group, tissue viability of ischemia/reperfusion limb in bFGF 10 and bFGF 50 group increased by 16 0% ( P <0 05) and 32 8% ( P <0 01), ATP content increased by 14 8% and 35 6% ( P <0 01), and plasma MDA level decreased by 45 2% and 56 2% ( P <0 01) 10?μg/kg bFGF had no significant effect on tissue water content, MPO activity, MDA concentration of ischemia/reperfusion limb, while 50?μg/kg of bFGF lowered these values by 15 7%, 32 5% and 13 6% ( P <0 05) and 14 7% ( P <0 01), MPO activity augmented by 44 9% and 96 1% ( P <0 01), ATP content decreased by 13 1% ( P <0 05) and 33 3% ( P <0 01) Plasma and tissue MDA concentrations in VEGF 10 group had no significant changes ( P >0 05), while in VEGF 50 group, these values were elevated by 46 4% and 38 6% ( P <0 01) Conclusion bFGF attenuated, while VEGF exacerbated ischemia/reperfusion injury of rat limb significantly, the mechanism of which was probably related to preventing or enhancing lipid peroxide, and increasing or decreasing energy store
文摘Objective To investigate the expression of endoplasmic reticulum stress(ESR)marker C/EBP homologous protein-10(CHOP-10)in the human aortic endothelial cells(HAEC)under the ischemia and hypoxia stress and to study the effects of atorvastatin on the process.Methods The cultured HAEC were divided into normal control group,ischemia/hypoxia model group。
基金Acknowledgments We thank Medjaden and Editage for its linguistic assistance during the preparation of this manuscript. Financial support and sponsorship This study was supported by the grants from National Natural Science Foundation of China （No. 81274109, 30973238）, Key Research Project of Beijing Natural Science Foundation （B）/Beijing Education Committee （No. KZ201010025024）, and Project for Science and Technology Innovation, Beijing Education Committee （No. PXM2011 014226 07 000085）.
文摘Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular diseases.This study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki disease.Methods：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time points.The protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,respectively.Nuclear factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot assay.Protein expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot assay.Results：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and activity.Furthermore,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 min.In addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 min.Conclusions：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.
基金supported by the Natural Science Foundation of Jiangsu Province(no.SBK2023021169 to H.Z.)the Jiangsu Vocational College of Medicine Campus Local Collaborative Innovation Research Project(no.20239701 to Y.M.)+1 种基金the 2024 Nanjing Health Technology Development Project(no.YKK24240 to Y.M.)Scientific Research Project of Jiangsu Provincial Health Commission(no.Z2023071 to S.X.).
文摘Background:Ischemic heart disease is a leading cause of mortality and disability worldwide among cardiovascular conditions.Myocardial ischemia-reperfusion injury(MIRI)occurs following percutaneous coronary intervention,during which neutrophils generate neutrophil extracellular traps(NETs)in response to injury.This study aims to elucidate the mechanisms underlying NET activation and its impact on MIRI.Methods:Sham and MIRI rat models were established.Various techniques,including enzyme-linked immunosorbent assay,hematoxylin and eosin staining,Masson staining,and transmission electron microscopy,were used to assess endothelial cell injury and myocardial tissue inflammation.Immunofluorescence was employed to evaluate NET activation in tissues,peripheral blood neutrophils,and protein colocalization.MitoTracker and ER-Tracker staining were conducted to assess the formation of mitochondria-associated membranes(MAMs).Extracted NETs were applied to conduct microvascular endothelial cell tube formation assay and flow cytometry.RNA-sequencing and immunoprecipitation-mass spectrometry were applied to determine the key regulators.Flow cytometry and Western blot were used to assess Ca^(2+)and mitophagy levels in neutrophils.Deoxyribonuclease I,NET inhibitor,was injected into MIRI rats to evaluate the in vivo effects of NET modulation on MIRI severity.Results:MIRI was often accompanied by cardiac microvascular endothelial cell(CMEC)injury and inflammation.Lactate mediated H3K18 lactylation at the MICU3 promoter in neutrophils,enhancing its transcription and leading to elevated MICU3 levels.Besides,lactate also promoted the interaction between MICU3 and AASR1,stabilizing MICU3 through lactylation.Up-regulated MICU3 interacted with VDAC1,facilitating MAM formation,excessive Ca^(2+)uptake,mitochondrial dysfunction,mitophagy activation,and NET activation.Elevated NET level exacerbated CMEC dysfunction,further aggravating MIRI.Conclusion:Lactate-driven MICU3 transcriptional activation and stabilization facilitates NET formation,contributing to MIRI development.
