Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the J...Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.展开更多
Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GN...Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].展开更多
Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequentl...Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.展开更多
In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause o...In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.展开更多
Vascular stents play an important role in the minimally invasive treatment of vascular diseases,such as vascular stenosis,vascular aneurysm,vascular dissection and vascular atherosclerotic plaque disease.Bare metal st...Vascular stents play an important role in the minimally invasive treatment of vascular diseases,such as vascular stenosis,vascular aneurysm,vascular dissection and vascular atherosclerotic plaque disease.Bare metal stents were initially fabricated;however,the incidence of complications such as thrombosis,inflammation,restenosis,vascular injury,displacement and endoleakage is still high after implantation.To overcome these complications,several strategies for designing functional vascular stents have been carried out.Drug-eluting stents,biodegradable stents and bionic stents were manufactured and investigated.This review aims to comprehensively analyze the vascular diseases suitable for stent implantation treatment,tissue reactions after implantation,the materials and manufacturing techniques used to fabricate vascular stents,the various application scenarios in which they could be used to treat vascular lesions and the development process of vascular stents.Future development trends of vascular stents are expected to prioritize their performance,biocompatibility,and clinical accessibility.The design of vascular stents may be transformed or improved to better fulfill the rehabilitation requirements of vascular disease patients.Finally,various application scenarios may be used to treat vascular or even nonvascular diseases via endovascular access.展开更多
Objective:Cold exposure may impair vascular function and promote cardiovascular diseases(CVDs)by causing vasoconstriction,hemodynamic changes,and sympathetic activation.Vascular aging,a key factor in CVDs,is linked to...Objective:Cold exposure may impair vascular function and promote cardiovascular diseases(CVDs)by causing vasoconstriction,hemodynamic changes,and sympathetic activation.Vascular aging,a key factor in CVDs,is linked to phenotypic switching of vascular smooth muscle cells(VSMCs),but its regulatory mechanisms are not fully understood.Materials and methods:We used aged C57BL/6 mice and D-galactose-induced senescent VSMCs to investigate the role of the E3 ligase RLIM in arterial aging.RLIM knockdown and overexpression in vivo were achieved using adeno-associated virus(AAV)vectors.Vascular aging and stiffness were assessed usingβ-galactosidase staining,pulse wave velocity(PWV)measurements,and histological staining.Proteomic profiling was conducted to identify key protein alterations associated with vascular dysfunction and to elucidate underlying mechanisms.Results:RLIM expression was significantly upregulated in the aortae of aged mice and D-galactose-induced senescent VSMCs.AAV-mediated RLIM knockdown significantly attenuated vascular aging,as evidenced by vascular ultrasound and histological assessments.Conversely,RLIM overexpression exacerbated vascular damage.Proteomic analysis revealed that RLIM knockdown in VSMCs from aged mice resulted in increased expression of smooth muscle contractile proteins and decreased levels of inflammatory markers,indicating a phenotypic shift toward a more contractile state.Conclusion:These findings identify RLIM as a key regulator of arterial aging and a promising therapeutic target for age-related cardiovascular diseases.展开更多
MANTA vascular closure device is an alternative vascular access closure device that is predominantly designed for large bore arteriotomy procedures.Its implementation to reduce morbidity and mortality following percut...MANTA vascular closure device is an alternative vascular access closure device that is predominantly designed for large bore arteriotomy procedures.Its implementation to reduce morbidity and mortality following percutaneous procedures including peripheral veno-arterial(VA)-extracorporeal membrane oxygenation(ECMO)in critically ill patients with various severe clinical conditions such as refractory cardiogenic shock remains to be under scientific discussion.The use of the MANTA vascular closure device leads to a sufficient reduction in a number of post-decannulation complications such as bleeding,vascular complications,inflammatory reactions and major amputation.Furthermore,the technical success of percutaneous decannulation of VA-ECMO with the MANTA vascular closure device appears to be safe and effective.It has been reported that MANTA vascular closure device exerted a strict similarity with other vascular surgical systems in safe profile regardless of the indication for its utilization.Overall,the immobilized patients achieved a favorable recovery outcome with MANTA including safe decannulation and low risk of vascular complications.The authors suggest the use of pulse wave distal Doppler technology for early detection of these clinically relevant complications.In conclusion,MANTA vascular closure device seems to be safe and effective technical approach to provide low-risk vascular assess for a long time for severe sick individuals.展开更多
Dear Editor,We describe a case diagnosed with exudative perifoveal vascular anomalous complex(ePVAC)successfully treated with focal laser photocoagulation(577 nm),achieving a favorable prognosis with best-corrected vi...Dear Editor,We describe a case diagnosed with exudative perifoveal vascular anomalous complex(ePVAC)successfully treated with focal laser photocoagulation(577 nm),achieving a favorable prognosis with best-corrected visual acuity(BCVA)of 20/20.Additionally,we discussed the identification of a possible early-onset non-ePVAC.The ePVAC is characterized as an isolated,aneurysmal abnormity near the macula and usually accompanied by cystic macular edema(ME)[1-2].展开更多
AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHO...AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.展开更多
Vascular calcification is closely associated with cardiovascular-related mortality,particularly high-risk of occurring this disease is in patients suffering from hypertension.Vascular calcification involves the active...Vascular calcification is closely associated with cardiovascular-related mortality,particularly high-risk of occurring this disease is in patients suffering from hypertension.Vascular calcification involves the active deposition of calcium and other mineral substances in the vascular wall.In blood vessels,intimal calcification is related to atherosclerosis,whereas medial calcification is a non-occlusive process that increases vascular stiffness and reduces vascular compliance.In the valves,calcification of the leaflets can change the mechanical properties of the tissue and result in stenosis.Cardiovascular diseases are being lead significant health risk worldwide and its estimated 30%of deaths.Synthetic drugs can help in the treatment of cardiovascular disease but they have limited efficacy and carry substantial risks.High risk and narrow margin of safety of synthetic drugs growing our interest to explore the different plants with specific medicinal properties in treatment of different cardiovascular disorders including hypertension,atherosclerosis,cardiac arrest and heart failure.Plants like Daucus carota,Nerium oleander,Amaranthus,Terminalia arjuna,and Picrorhiza kurroa contain phytochemicals like tea flavonoids,polyphenols,plant sterols,and terpenoids that can prevent low density lipoprotein cholesterol oxidation,inhibit cholesterol synthesis and promote vasodilation.Researchers has identified many medicinal herbs and their chemical components that show potential in alleviating vascular calcification via antioxidant mechanisms.In this study,we briefly discuss the role of vascular calcification in the pathophysiology of cardiac diseases.Utilizing the efficacy of these natural molecules will lead to the development of new treatment methods for chronic heart disease associated with vascular calcification.展开更多
Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT paramet...Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT parameters measured using coronary computed tomography have emerged as potential noninvasive imaging biomarkers for quantifying coronary artery inflammation,with significant clinical value in the early detection,disease progression assessment,treatment efficacy evaluation,and prognosis prediction of cardiovascular diseases.Furthermore,new technologies such as PCAT radiomics analysis have broadened its potential applications in evaluating coronary plaque vulnerability,predicting cardiovascular events,and improving risk stratification.This review discusses recent advances in PCAT research,focusing on its role in coronary artery disease risk identification and inflammation monitoring,and aims to offer imaging-based insights to support its future clinical use in cardiovascular disease management.展开更多
AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy...AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy(cCSC)eyes with macular neovascularization(MNV)using ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:This retrospective comparative study included 46 cCSC with MNV eyes(With MNV group),52 cCSC without MNV eyes(Without MNV group),and 40 age-matched healthy controls.UWF SS-OCTA imaging with a 20 mm×24 mm protocol was used to quantify CVI across 9 subfields(superotemporal,superior,superonasal,temporal,central,nasal,inferotemporal,inferior,and inferonasal).The CVI was compared among the groups.RESULTS:With MNV group demonstrated significantly older mean age than Without MNV group(56.2±6.1 vs 47.5±8.6y,P<0.001).The CVI was significantly lower in the With MNV group than in the Without MNV group,except in the superotemporal,superior,and temporal regions(all P<0.05).Notably,despite MNV-associated CVI reductions,the With MNV group maintained a higher CVI than the control group in all 5 subfields(superior,temporal,central,inferior,and inferonasal;all P<0.05).In the central region,CONCLUSION:CVI decreases,and choroidal structural changes extend beyond the subfoveal area in cCSC with MNV eyes,providing with an imaging evidence for the important role of choroidal ischemia in the pathogenesis of MNV in cCSC.展开更多
Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease.The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's d...Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease.The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease.Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discove ry of novel targets for intervention.We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls,revealing obvious changes in vascular function.CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients,with altered intercellular communication of endothelial cells and pericytes being the most prominent.Differentially expressed genes were also identified.Using the CellChat results,AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor(VEGF)A-VEGF receptor(VEGFR)2 pathway.AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity.Two subtypes of middle temporal gyrus cells showed significant alteration in AD:endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4(ERBB4^(high))and pericytes with high expression of angiopoietin-like 4(ANGPTL4^(high)).Finally,combining bulk RNA sequencing data and two machine learning algorithms(least absolute shrinkage and selection operator and random forest),four characteristic Alzheimer's disease feature genes were identified:somatostatin(SST),protein tyrosine phosphatase non-receptor type 3(PTPN3),glutinase(GL3),and tropomyosin 3(PTM3).These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway.Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus.In conclusion,this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease.These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.展开更多
Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide...Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.展开更多
BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are e...BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are exceedingly infrequent.Notwithstanding,patients with copious comorbidities should be carefully monitored for potential vascular injury.CASE SUMMARY This case report presents the management of a 75-year-old male patient with a history of diabetes mellitus and arterial hypertension who was admitted to the emergency room with a superior pubic ramus fracture.The patient experienced a significant drop in hematocrit and hemoglobin levels post-admission,necessi-tating urgent intervention.A computed tomography angiography revealed active bleeding,leading to the embolization of the medial femoral branch.The patient was stabilized hemodynamically and was discharged after 15 days,with recom-mendations for home-based follow-up care.CONCLUSION This report denotes the various challenges and strategies in managing simple fractures that are treated conservatively,but need prompt monitoring for occult vascular injuries that can be fatal.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
文摘Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
基金supported by the Natural Science Foundation of Guangdong Province(2022A1515010297)the National Natural Science Foundation of China(32100765)+1 种基金the Xiamen Medical Health Science and Technology Project(3502Z20194098)the Shenzhen-Hong Kong-Macao Science and Technology Innovation Project(SGDX2020110309280100).
文摘Dear Editor,Sturge-Weber Syndrome(SWS)is a rare congenital neurocutaneous syndrome[1,2],with an estimated prevalence of 0.19 in 100,000 annually[3].It is a non-hereditary disease linked to a somatic mutation in the GNAQ,GNA11,or GNB2 gene[1],leading to vascular malformations in the cutaneous forehead,cerebral cortex,and eye[1,2].Notably,~70%of pediatric patients diagnosed with SWS exhibit brain calcification(BC)[4],though the prevalence of BC ranges from only 1%in young individuals to>20%in the senior population(>60 years old)[5].Similar to the elderly,BC in pediatric SWS patients is identified as vascular calcification[6,7],whereas BC in pediatric patients with tuberous sclerosis and tumors has been previously described as dystrophic calcification[6].
基金Supported by Science and Technology Department of Yunnan Province-Kunming Medical University,Kunming Medical Joint Special Project-Surface Project,No.202401AY070001-164Yunnan Provincial Clinical Research Center Cardiovascular Diseases-New Technology Research for Development Project for Diagnosis and Treatment Cardiovascular Diseases,No.202102AA310002the Key Technology Research and Device Development Project for Innovative Diagnosis and Treatment of Structural Heart Disease in the Southwest Plateau Region,No.202302AA310045.
文摘Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.
文摘In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.
基金supported by Natural Science Foundation of China(No.31930067)Natural Science Foundation of Sichuan Province(No.23NSFSC5880)+2 种基金Chengdu Medical Research Project(No.2022004)Natural Science Foundation of Clinical Medical College and Affiliated Hospital of Chengdu University(No.Y202206)Postdoctoral Research and Development Fund of West China Hospital,Sichuan University(No.2023HXBH052).
文摘Vascular stents play an important role in the minimally invasive treatment of vascular diseases,such as vascular stenosis,vascular aneurysm,vascular dissection and vascular atherosclerotic plaque disease.Bare metal stents were initially fabricated;however,the incidence of complications such as thrombosis,inflammation,restenosis,vascular injury,displacement and endoleakage is still high after implantation.To overcome these complications,several strategies for designing functional vascular stents have been carried out.Drug-eluting stents,biodegradable stents and bionic stents were manufactured and investigated.This review aims to comprehensively analyze the vascular diseases suitable for stent implantation treatment,tissue reactions after implantation,the materials and manufacturing techniques used to fabricate vascular stents,the various application scenarios in which they could be used to treat vascular lesions and the development process of vascular stents.Future development trends of vascular stents are expected to prioritize their performance,biocompatibility,and clinical accessibility.The design of vascular stents may be transformed or improved to better fulfill the rehabilitation requirements of vascular disease patients.Finally,various application scenarios may be used to treat vascular or even nonvascular diseases via endovascular access.
基金the National Natural Science Foundation of China(82273919)the HMU Marshal Initiative Funding(HMUMIF-21022).
文摘Objective:Cold exposure may impair vascular function and promote cardiovascular diseases(CVDs)by causing vasoconstriction,hemodynamic changes,and sympathetic activation.Vascular aging,a key factor in CVDs,is linked to phenotypic switching of vascular smooth muscle cells(VSMCs),but its regulatory mechanisms are not fully understood.Materials and methods:We used aged C57BL/6 mice and D-galactose-induced senescent VSMCs to investigate the role of the E3 ligase RLIM in arterial aging.RLIM knockdown and overexpression in vivo were achieved using adeno-associated virus(AAV)vectors.Vascular aging and stiffness were assessed usingβ-galactosidase staining,pulse wave velocity(PWV)measurements,and histological staining.Proteomic profiling was conducted to identify key protein alterations associated with vascular dysfunction and to elucidate underlying mechanisms.Results:RLIM expression was significantly upregulated in the aortae of aged mice and D-galactose-induced senescent VSMCs.AAV-mediated RLIM knockdown significantly attenuated vascular aging,as evidenced by vascular ultrasound and histological assessments.Conversely,RLIM overexpression exacerbated vascular damage.Proteomic analysis revealed that RLIM knockdown in VSMCs from aged mice resulted in increased expression of smooth muscle contractile proteins and decreased levels of inflammatory markers,indicating a phenotypic shift toward a more contractile state.Conclusion:These findings identify RLIM as a key regulator of arterial aging and a promising therapeutic target for age-related cardiovascular diseases.
文摘MANTA vascular closure device is an alternative vascular access closure device that is predominantly designed for large bore arteriotomy procedures.Its implementation to reduce morbidity and mortality following percutaneous procedures including peripheral veno-arterial(VA)-extracorporeal membrane oxygenation(ECMO)in critically ill patients with various severe clinical conditions such as refractory cardiogenic shock remains to be under scientific discussion.The use of the MANTA vascular closure device leads to a sufficient reduction in a number of post-decannulation complications such as bleeding,vascular complications,inflammatory reactions and major amputation.Furthermore,the technical success of percutaneous decannulation of VA-ECMO with the MANTA vascular closure device appears to be safe and effective.It has been reported that MANTA vascular closure device exerted a strict similarity with other vascular surgical systems in safe profile regardless of the indication for its utilization.Overall,the immobilized patients achieved a favorable recovery outcome with MANTA including safe decannulation and low risk of vascular complications.The authors suggest the use of pulse wave distal Doppler technology for early detection of these clinically relevant complications.In conclusion,MANTA vascular closure device seems to be safe and effective technical approach to provide low-risk vascular assess for a long time for severe sick individuals.
基金Supported by the 1.3.5 Project of West China Hospital of Sichuan University(No.2023HXFH043)Sichuan Natural Science Foundation(No.24NSFSC1718).
文摘Dear Editor,We describe a case diagnosed with exudative perifoveal vascular anomalous complex(ePVAC)successfully treated with focal laser photocoagulation(577 nm),achieving a favorable prognosis with best-corrected visual acuity(BCVA)of 20/20.Additionally,we discussed the identification of a possible early-onset non-ePVAC.The ePVAC is characterized as an isolated,aneurysmal abnormity near the macula and usually accompanied by cystic macular edema(ME)[1-2].
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.
文摘Vascular calcification is closely associated with cardiovascular-related mortality,particularly high-risk of occurring this disease is in patients suffering from hypertension.Vascular calcification involves the active deposition of calcium and other mineral substances in the vascular wall.In blood vessels,intimal calcification is related to atherosclerosis,whereas medial calcification is a non-occlusive process that increases vascular stiffness and reduces vascular compliance.In the valves,calcification of the leaflets can change the mechanical properties of the tissue and result in stenosis.Cardiovascular diseases are being lead significant health risk worldwide and its estimated 30%of deaths.Synthetic drugs can help in the treatment of cardiovascular disease but they have limited efficacy and carry substantial risks.High risk and narrow margin of safety of synthetic drugs growing our interest to explore the different plants with specific medicinal properties in treatment of different cardiovascular disorders including hypertension,atherosclerosis,cardiac arrest and heart failure.Plants like Daucus carota,Nerium oleander,Amaranthus,Terminalia arjuna,and Picrorhiza kurroa contain phytochemicals like tea flavonoids,polyphenols,plant sterols,and terpenoids that can prevent low density lipoprotein cholesterol oxidation,inhibit cholesterol synthesis and promote vasodilation.Researchers has identified many medicinal herbs and their chemical components that show potential in alleviating vascular calcification via antioxidant mechanisms.In this study,we briefly discuss the role of vascular calcification in the pathophysiology of cardiac diseases.Utilizing the efficacy of these natural molecules will lead to the development of new treatment methods for chronic heart disease associated with vascular calcification.
基金Supported by the Health Commission of the Sichuan Province Medical Science and Technology Program,China,No.24WXXT10the Sichuan Province Science and Technology Support Program,China,No.2021YJ0242the 23rd Batch of Student Scientific Research Project Approval of Jiangsu University,China,No.Y23A164.
文摘Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT parameters measured using coronary computed tomography have emerged as potential noninvasive imaging biomarkers for quantifying coronary artery inflammation,with significant clinical value in the early detection,disease progression assessment,treatment efficacy evaluation,and prognosis prediction of cardiovascular diseases.Furthermore,new technologies such as PCAT radiomics analysis have broadened its potential applications in evaluating coronary plaque vulnerability,predicting cardiovascular events,and improving risk stratification.This review discusses recent advances in PCAT research,focusing on its role in coronary artery disease risk identification and inflammation monitoring,and aims to offer imaging-based insights to support its future clinical use in cardiovascular disease management.
基金Supported by General Program of National Natural Science Foundation of China(No.82471110)National Key Research and Development Program of China(No.2022YFC2502805)Postdoctoral Foundation of General Hospital of Central Theater Command(No.20210517KY04).
文摘AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy(cCSC)eyes with macular neovascularization(MNV)using ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:This retrospective comparative study included 46 cCSC with MNV eyes(With MNV group),52 cCSC without MNV eyes(Without MNV group),and 40 age-matched healthy controls.UWF SS-OCTA imaging with a 20 mm×24 mm protocol was used to quantify CVI across 9 subfields(superotemporal,superior,superonasal,temporal,central,nasal,inferotemporal,inferior,and inferonasal).The CVI was compared among the groups.RESULTS:With MNV group demonstrated significantly older mean age than Without MNV group(56.2±6.1 vs 47.5±8.6y,P<0.001).The CVI was significantly lower in the With MNV group than in the Without MNV group,except in the superotemporal,superior,and temporal regions(all P<0.05).Notably,despite MNV-associated CVI reductions,the With MNV group maintained a higher CVI than the control group in all 5 subfields(superior,temporal,central,inferior,and inferonasal;all P<0.05).In the central region,CONCLUSION:CVI decreases,and choroidal structural changes extend beyond the subfoveal area in cCSC with MNV eyes,providing with an imaging evidence for the important role of choroidal ischemia in the pathogenesis of MNV in cCSC.
基金supported by the Natural Science Foundation of Shanxi Province,No.20210302123299The Belt and Road Program of Shanxi Province,No.110000261420228002(both to CZ)。
文摘Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease.The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease.Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discove ry of novel targets for intervention.We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls,revealing obvious changes in vascular function.CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients,with altered intercellular communication of endothelial cells and pericytes being the most prominent.Differentially expressed genes were also identified.Using the CellChat results,AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor(VEGF)A-VEGF receptor(VEGFR)2 pathway.AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity.Two subtypes of middle temporal gyrus cells showed significant alteration in AD:endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4(ERBB4^(high))and pericytes with high expression of angiopoietin-like 4(ANGPTL4^(high)).Finally,combining bulk RNA sequencing data and two machine learning algorithms(least absolute shrinkage and selection operator and random forest),four characteristic Alzheimer's disease feature genes were identified:somatostatin(SST),protein tyrosine phosphatase non-receptor type 3(PTPN3),glutinase(GL3),and tropomyosin 3(PTM3).These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway.Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus.In conclusion,this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease.These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.
基金supported by the National Natural Science Foundation of China(Nos.82200379 and 82300309)the Shanghai Sailing Program(No.22YF1443100)+1 种基金the Academy Talent Special Fund of The First Affiliated Hospital of Nanjing Medical University(Nos.YNRCQN0312 and MXJL202208)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB592),China.
文摘Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.
文摘BACKGROUND Pubic ramus fractures are generally considered fragility fractures in the elderly population,commonly deriving from a low-impact fall.Treatment is ordinarily conservative and hemodynamic complications are exceedingly infrequent.Notwithstanding,patients with copious comorbidities should be carefully monitored for potential vascular injury.CASE SUMMARY This case report presents the management of a 75-year-old male patient with a history of diabetes mellitus and arterial hypertension who was admitted to the emergency room with a superior pubic ramus fracture.The patient experienced a significant drop in hematocrit and hemoglobin levels post-admission,necessi-tating urgent intervention.A computed tomography angiography revealed active bleeding,leading to the embolization of the medial femoral branch.The patient was stabilized hemodynamically and was discharged after 15 days,with recom-mendations for home-based follow-up care.CONCLUSION This report denotes the various challenges and strategies in managing simple fractures that are treated conservatively,but need prompt monitoring for occult vascular injuries that can be fatal.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
