Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disabili...Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
Objective:To explore the value of TCD and CDUS on diagnosis of large artery atherosclerosis.Methods:In our study,90 patients who had been admitted to our hospital and diagnosed as LAA according to CISS typing were sel...Objective:To explore the value of TCD and CDUS on diagnosis of large artery atherosclerosis.Methods:In our study,90 patients who had been admitted to our hospital and diagnosed as LAA according to CISS typing were selected as the research object.A retrospective analysis was conducted,using CTA as golden standard for diagnoses of stenoses.Explore the risk factors of LAA,the reliability of TCD and CDUS in diagnosis of the stenosis and distribution of stenosis in each vessel.Results:Hypertension and type 2 diabetes are risk factors of LAA vascular stenosis.Middle cerebral artery stenosis detection by TCD carries the highest reliability(sensitivity 90.91%,specificity 97.89%,positive predictive value 96.15%,the negative predictive value was 94.9%,the positive likelihood ratio was 43.18,negative likelihood ratio 0.09,Kappa=0.9).The consistency of TCD is as good as CTA in head and neck part.The negative coincidence rate was higher in the anterior circulation vessels(97.98%),followed by the coincidence rate of severe stenosis(95.23%).However,the detection rate of posterior circulation vessels positive,moderate and severe stenosis,mild stenosis gradually decreased by TCD.CDUS carries general reliability in detecting intracranial extracranial stenosis,the highest reliability in internal carotid artery(kappa 0.82),and the worst consistency in vertebral artery(kappa 0.38).The negative coincidence rate of CDUS in extracranial cerebrovascular stenosis was highest(97.22),followed by the overall compliance rate(91.55%).242 branches of vascular stenosis were discovered in our study,among which intracranial artery stenosis 61.15%(148/242)is higher than that in extracranial artery 38.85%(90/242),ratio of moderate to severe stenosis is as high as 82.23%(199/242).Intracranial artery stenosis in ICA is extremely common(51.11%,46/90),and MCA is the common area of intracranial artery stenosis(37.16%,55/148).Conclusions:(1)Hypertension,type 2 diabetes are risk factors for LAA stenosis.(2)TCD detection of intracranial vascular stenosis carries the best consistency,and reliability of MCA is the highest.In our search,MCA possesses the highest rate of stenosis,and negative coincidence rate by TCD examination was the highest,which could be used for screening method for stenosis.The reliability of TCD in diagnosis of moderate and severe stenosis was relatively better than mild stenosis.(3)CDUS detection of anterior circulation lesions is better than that of posterior circulation lesions.Evaluate effect on moderate and severe stenosis was better than that of mild one.The ratio of ICA stenosis was the highest,but the effect on VA was poor.(4)The incidence of intracranial vascular stenosis is more common than that of the intracranial vascular stenosis.展开更多
Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, th...Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.展开更多
Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment fo...Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.展开更多
Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospectiv...Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospective study of patients admitted at neurology department of Yalgado Ouedraogo University Teaching Hospital with ischemic stroke and cerebral large vessel atherosclerosis in the period from January 1, 2012 to December 31, 2016. Results: The prevalence of extracranial carotid atherosclerosis was 23.9%. The mean age of patients was 63.5 years (Range 31 - 90 years). The study population included 65% of men and 35% of women. Hypertension was the most common vascular risk factor (75.6%). Stroke was mostly located in the anterior circulation in 23.9%. Low HDL-C was present in 52% of patients. The majority of plaque was homogeneous (85.2%). Plaque were located in carotid bulbar artery (38.5%) followed by common carotid artery (28.2%) and extracranial internal carotid artery (18.6%). According to cerebral lesion, plaque was bilateral in 45.5%, ipsilateral in 42.3% and contralateral in 12.1% of cases. Tight stenosis was found in 30.1% of patients. There was a significant link between male gender and tight stenosis (p = 0.004). Aspirin was the most antiplatelet therapy used (95.5%). Statin therapy was used in 91% of patients. The mean duration of hospitalization was 12.5 days with a mortality rate of 7.1%. Conclusions: Our study showed that extra carotid atherosclerosis was the most common cause of ischemic stroke in Burkina Faso. Man gender was most represented than women.展开更多
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato...BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.展开更多
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis.However,nearly all nucleic acid delivery systems developed for atherosclerosis necessi-tate injection,which re...Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis.However,nearly all nucleic acid delivery systems developed for atherosclerosis necessi-tate injection,which results in rapid elimination and poor patient compliance.Consequently,oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics.Herein we report the development of yeast-derived capsules(YCs)packaging an antisense oligonucleotide(AM33)targeting microRNA-33(miR-33)for the oral treatment of atherosclerosis.YCs provide stability for AM33,preventing its premature release in the gastrointestinal tract.AM33-containing YCs,defined as YAM33,showed high transfection in macrophages,thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33.Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE^(-/-)mice,primarily by transepithelial absorption via M cells in Peyer’s patches and subsequent translocation via macrophages through the lymphatic sys-tem.Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis.More-over,oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects.Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids,either alone or in combination with existing drugs,offering a promising approach for precision therapy of atherosclerotic diseases.展开更多
Atherosclerosis,which is defined by plaque accumulation within artery walls,is one of the leading causes of cardiovascular disease and mortality.Although they help control symptoms and slow the condition’s progressio...Atherosclerosis,which is defined by plaque accumulation within artery walls,is one of the leading causes of cardiovascular disease and mortality.Although they help control symptoms and slow the condition’s progression,traditional treatments,including medication,surgery,and lifestyle changes,do not ad dress the underlying pathophysiology.Recent innovations in targeted cell therapy,such as gene editing,stem cell therapy,and exosome-based therapies,present encouraging methods for repairing endothelium damage,lowering in-flammation,and restoring vascular health.This study examines how different therapy approaches are related,highlighting the potential of regenerative medicine to stop the progression of atherosclerosis.Despite the potential of these developments,issues such as financial constraints,regulatory obstacles,patient-specific efficacy variability,and safety concerns must be resolved.More research and technical developments are essential to incorporate these treatments into clinical practice,improve patient outcomes,and reduce the prevalence of cardiovascular disease worldwide.展开更多
Objective: The aim of this study was to determine the influence of long-term low-dose hor mone replacement therapy (HRT) on the intima-media wall of the carotid artery in postmenopa usal women by ultrasound.Methods: 1...Objective: The aim of this study was to determine the influence of long-term low-dose hor mone replacement therapy (HRT) on the intima-media wall of the carotid artery in postmenopa usal women by ultrasound.Methods: 146 postmenopausal women were divided into the HRT group(n= 68, HRT over 5years after menopause) and the control group(n= 78, no HRT). The intima-media thickness (IMT) of the carotid arteries was measured bilaterally, the characteristics of the atherosclerotic plaques were described, the peak systolic velocity (PSV) and resistance index (RI) were measured by ultrasound examination.Results: The IMT of HRT group was significantly smaller than that of the control group,(0. 089±0. 22) cm vs (0. 093±0.29) cm, (P＜0. 01). The occurrence of plaques was reduced in HRT group than the control group (7.7% vs 12.7%, P＜0. 05). The plaques were most frequently found at the bifurcation of the arteries. The soft and mixed plaques in HRT group were found significantly less than that of the control group (soft 1.7% vs 4. 5%, mixed 3.1% vs 6. 7%, both P＜0.05), while the hard plaques in HRT group were more than those of the control group(2.6% vs 1.3%, P＜0. 05). The maximum plaque thickness of HRT group was less than that of control group (0. 191±0. 057) cm vs (0. 226±0. 073) cm, (P＜0.05). The internal carotid artery PSV and RI in the two groups were similar [PSV (65.61±26.55) cm/s vs (64.82±27. 22) cm/s, RI (0.67±0. 082) vs (0. 68±0. 075), both P＞0.05].Conclusion: Our study indicated that HRT may has an effect to reduce the carotid IMT thickness, inhibit the plaque formation, and make the plaques harder and more stable. The long-term low-dose HRT may protect the postmenopausal women against the artherosclerosis of the carotid artery.展开更多
The recent shift of the concept of cardiovascular disease as a chronic progressive condition,potentially involving multiple districts,has driven attention to the optimal management of patients with concomitant coronar...The recent shift of the concept of cardiovascular disease as a chronic progressive condition,potentially involving multiple districts,has driven attention to the optimal management of patients with concomitant coronary and peripheral artery disease,representing a subset of patients with an increased risk of events and impaired survival.Recent pharmacological achievements in terms of antithrombotic therapy and lipid-lowering drugs allow multiple therapeutical combinations,thus requiring optimizing the treatment in a tailored fashion according to patients’risk profiles.Nevertheless,data dedicated to this specific subset of patients are still modest.We summarize currently available strategies and indications for the management of antithrombotic and lipid-lowering drugs in patients with the poly-vascular disease.展开更多
For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of H...For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.展开更多
The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipopro...The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is an absolute requirement for lesion development. This allows us to consider intracellular cholesterol retention as a novel target for anti-atherosclerotic therapy. In this case, the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review summarizes the results of our basic studies shedding light on the mechanisms of intracellular cholesterol retention. We describe our cellular models to search for anti-atherosclerotic agents and demonstrate the use of these models for the development of anti-atherosclerotic drugs. We use natural products as the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy should be long-term or even lifelong. Using cellular models and natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured subendothelial aortic cells. We have developed drugs that reduce intracellular cholesterol retention, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinics. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.展开更多
Coronary artery disease(CAD)is the leading cause of death worldwide,but because of several factors,one of which is antiplatelet therapy,the mortality rates have steadily declined.However,women continue to experience h...Coronary artery disease(CAD)is the leading cause of death worldwide,but because of several factors,one of which is antiplatelet therapy,the mortality rates have steadily declined.However,women continue to experience higher CAD mortality rates than men.This may be explained by differences in comorbidities,increased time to presentation,higher bleeding rates,and differences in management.There are numerous landmark trials in the field of antiplatelet therapy;however,women are consistently underrepresented in these trials.The results of these trials reveal that women experience the same benefit as men from antiplatelet therapy but experience higher bleeding rates;therefore bleeding-reduction strategies are imperative in this patient population.This review provides an overview of the available evidence on CAD in women and its implications for antiplatelet medications.展开更多
Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular c...Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular cholesterol retention is the principal event in the genesis of atherosclerotic lesions. This allows us to consider cellular retention of cholesterol as a novel target for anti-atherosclerotic therapy. In this case the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review describes our approach based on the use of cultured human arterial cells for the development of direct anti-atherosclerotic therapy. We use natural products as the basis of promising drugs for anti-atherosclerotic therapy. Using natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured cells. Our knowledge of the mechanisms of atherosclerosis is the foundation on which we have developed drugs that have a direct anti-atherosclerotic effect, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with allicor or inflaminat has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Karinat prevents the development of carotid atherosclerosis in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinical practice. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.展开更多
Objective： To explore the efficacy of interventional therapy for chronic atherosclerotic occlusive disease of the lower extremity. Methods： Fifty-six cases of simple atherosclerotic occlusive disease of lower extrem...Objective： To explore the efficacy of interventional therapy for chronic atherosclerotic occlusive disease of the lower extremity. Methods： Fifty-six cases of simple atherosclerotic occlusive disease of lower extremity were divided into 3 types according to the location of occhision, including 17 cases of abdominal aorta-iliac artery, 18 cases of iliac-femoral artery, and 21 cases of inferior popliteal artery. Catheter and guide wire combined with blunt dissection and subtle banding were used to dredge the occluded vessels, and stents were implanted when interlayer appeared. Results： After the treatment, 46 cases of occlusion were dredged （82.1%）, 6 cases remained occluded with the same symptoms （10.7%）, and 4 cases had severer symptoms （7.1%）. Among the 46 successful cases, there were 16 cases of abdominal aorta-iliac artery （94.1%）, 16 cases of iliac-femoral artery （88.9%） and 14 cases of inferior popliteal artery, artery （66.6%）. There was no statistical difference between the abdominal aorta-iliac artery cases and iliac-femoral artery cases （P〉0.05）, but there was statistical difference between these two types and the inferior popliteal artery cases （P〈0.05）. In the successful cases, 9 cases of abdominal aorta-iliac artery （52.9%）, 10 cases of iliac-femoral artery （55.5%） and 10 cases of inferior popliteal artery （33.3%） had 5-10 cm of occlusion, with no statistical difference between the first two types （P〉0.05）, but with statistical difference between the first two types and the third type （P〈0.05）. Compared with the 14 dredged cases （71.4%）, the 7 cases （33.3%） of inferior popliteal artery cases had richer compensatory circulation （P〈0.05）. Conclusion： It＇s safe and effective to treat simple atherosclerotic occlusive disease of the lower extremity with interventional therapy. The location and length of occlusion and the abundance of compensatory circulation had effect on the therapy.展开更多
基金support from the Natural Science Foundation of Henan,China(Grant No.:202300410446)the National Natural Science Foundation of China(Grant No.:82071950).
文摘Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
文摘Objective:To explore the value of TCD and CDUS on diagnosis of large artery atherosclerosis.Methods:In our study,90 patients who had been admitted to our hospital and diagnosed as LAA according to CISS typing were selected as the research object.A retrospective analysis was conducted,using CTA as golden standard for diagnoses of stenoses.Explore the risk factors of LAA,the reliability of TCD and CDUS in diagnosis of the stenosis and distribution of stenosis in each vessel.Results:Hypertension and type 2 diabetes are risk factors of LAA vascular stenosis.Middle cerebral artery stenosis detection by TCD carries the highest reliability(sensitivity 90.91%,specificity 97.89%,positive predictive value 96.15%,the negative predictive value was 94.9%,the positive likelihood ratio was 43.18,negative likelihood ratio 0.09,Kappa=0.9).The consistency of TCD is as good as CTA in head and neck part.The negative coincidence rate was higher in the anterior circulation vessels(97.98%),followed by the coincidence rate of severe stenosis(95.23%).However,the detection rate of posterior circulation vessels positive,moderate and severe stenosis,mild stenosis gradually decreased by TCD.CDUS carries general reliability in detecting intracranial extracranial stenosis,the highest reliability in internal carotid artery(kappa 0.82),and the worst consistency in vertebral artery(kappa 0.38).The negative coincidence rate of CDUS in extracranial cerebrovascular stenosis was highest(97.22),followed by the overall compliance rate(91.55%).242 branches of vascular stenosis were discovered in our study,among which intracranial artery stenosis 61.15%(148/242)is higher than that in extracranial artery 38.85%(90/242),ratio of moderate to severe stenosis is as high as 82.23%(199/242).Intracranial artery stenosis in ICA is extremely common(51.11%,46/90),and MCA is the common area of intracranial artery stenosis(37.16%,55/148).Conclusions:(1)Hypertension,type 2 diabetes are risk factors for LAA stenosis.(2)TCD detection of intracranial vascular stenosis carries the best consistency,and reliability of MCA is the highest.In our search,MCA possesses the highest rate of stenosis,and negative coincidence rate by TCD examination was the highest,which could be used for screening method for stenosis.The reliability of TCD in diagnosis of moderate and severe stenosis was relatively better than mild stenosis.(3)CDUS detection of anterior circulation lesions is better than that of posterior circulation lesions.Evaluate effect on moderate and severe stenosis was better than that of mild one.The ratio of ICA stenosis was the highest,but the effect on VA was poor.(4)The incidence of intracranial vascular stenosis is more common than that of the intracranial vascular stenosis.
基金financial support from the Young Elite Scientists Sponsorship Program by Tianjin (No. 0701320001)Major Special Project of Tianjin (No. 0402080005)+1 种基金Program for Excellent Innovative Talents in Universities of Hebei Province (No. BJ2021019)Vietnam National University,Ho Chi Minh City (VNU-HCM,NCM2020-28-01)。
文摘Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.
文摘Intracranial atherosclerotic disease (ICAD) represents a major cause of stroke and transient ischemic attacks. The prevalence and natural course of ICAD are closely related to race and ethnicity. The best treatment for ICAD is a crucial issue;data from recent trials indicate that aggressive medical management and life style modifications are better than endovascular treatments for prevention of recurrent stroke in high-risk patients with ICAD. Endovascular treatment is still an option for subgroup of patients who are not responded to optimal medical therapy.
文摘Objective: To determine the prevalence and risk factors of carotid atherosclerosis among ischemic stroke patients in a tertiary hospital in Burkina Faso. Methodology: This was a descriptive and analytical retrospective study of patients admitted at neurology department of Yalgado Ouedraogo University Teaching Hospital with ischemic stroke and cerebral large vessel atherosclerosis in the period from January 1, 2012 to December 31, 2016. Results: The prevalence of extracranial carotid atherosclerosis was 23.9%. The mean age of patients was 63.5 years (Range 31 - 90 years). The study population included 65% of men and 35% of women. Hypertension was the most common vascular risk factor (75.6%). Stroke was mostly located in the anterior circulation in 23.9%. Low HDL-C was present in 52% of patients. The majority of plaque was homogeneous (85.2%). Plaque were located in carotid bulbar artery (38.5%) followed by common carotid artery (28.2%) and extracranial internal carotid artery (18.6%). According to cerebral lesion, plaque was bilateral in 45.5%, ipsilateral in 42.3% and contralateral in 12.1% of cases. Tight stenosis was found in 30.1% of patients. There was a significant link between male gender and tight stenosis (p = 0.004). Aspirin was the most antiplatelet therapy used (95.5%). Statin therapy was used in 91% of patients. The mean duration of hospitalization was 12.5 days with a mortality rate of 7.1%. Conclusions: Our study showed that extra carotid atherosclerosis was the most common cause of ischemic stroke in Burkina Faso. Man gender was most represented than women.
文摘BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.
基金supported by the National Natural Science Foun-dation of China,China(Nos.32301198 and 32271451)China Postdoctoral Science Foundation,China(No.2022M713832)+2 种基金Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX0939)New Chongqing Youth Innovative Talent Program(No.CSTB2024NSCQ-QCXMX0005)Graduate Supervisor Team Program of Chongqing in 2022.
文摘Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis.However,nearly all nucleic acid delivery systems developed for atherosclerosis necessi-tate injection,which results in rapid elimination and poor patient compliance.Consequently,oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics.Herein we report the development of yeast-derived capsules(YCs)packaging an antisense oligonucleotide(AM33)targeting microRNA-33(miR-33)for the oral treatment of atherosclerosis.YCs provide stability for AM33,preventing its premature release in the gastrointestinal tract.AM33-containing YCs,defined as YAM33,showed high transfection in macrophages,thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33.Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE^(-/-)mice,primarily by transepithelial absorption via M cells in Peyer’s patches and subsequent translocation via macrophages through the lymphatic sys-tem.Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis.More-over,oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects.Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids,either alone or in combination with existing drugs,offering a promising approach for precision therapy of atherosclerotic diseases.
文摘Atherosclerosis,which is defined by plaque accumulation within artery walls,is one of the leading causes of cardiovascular disease and mortality.Although they help control symptoms and slow the condition’s progression,traditional treatments,including medication,surgery,and lifestyle changes,do not ad dress the underlying pathophysiology.Recent innovations in targeted cell therapy,such as gene editing,stem cell therapy,and exosome-based therapies,present encouraging methods for repairing endothelium damage,lowering in-flammation,and restoring vascular health.This study examines how different therapy approaches are related,highlighting the potential of regenerative medicine to stop the progression of atherosclerosis.Despite the potential of these developments,issues such as financial constraints,regulatory obstacles,patient-specific efficacy variability,and safety concerns must be resolved.More research and technical developments are essential to incorporate these treatments into clinical practice,improve patient outcomes,and reduce the prevalence of cardiovascular disease worldwide.
文摘Objective: The aim of this study was to determine the influence of long-term low-dose hor mone replacement therapy (HRT) on the intima-media wall of the carotid artery in postmenopa usal women by ultrasound.Methods: 146 postmenopausal women were divided into the HRT group(n= 68, HRT over 5years after menopause) and the control group(n= 78, no HRT). The intima-media thickness (IMT) of the carotid arteries was measured bilaterally, the characteristics of the atherosclerotic plaques were described, the peak systolic velocity (PSV) and resistance index (RI) were measured by ultrasound examination.Results: The IMT of HRT group was significantly smaller than that of the control group,(0. 089±0. 22) cm vs (0. 093±0.29) cm, (P＜0. 01). The occurrence of plaques was reduced in HRT group than the control group (7.7% vs 12.7%, P＜0. 05). The plaques were most frequently found at the bifurcation of the arteries. The soft and mixed plaques in HRT group were found significantly less than that of the control group (soft 1.7% vs 4. 5%, mixed 3.1% vs 6. 7%, both P＜0.05), while the hard plaques in HRT group were more than those of the control group(2.6% vs 1.3%, P＜0. 05). The maximum plaque thickness of HRT group was less than that of control group (0. 191±0. 057) cm vs (0. 226±0. 073) cm, (P＜0.05). The internal carotid artery PSV and RI in the two groups were similar [PSV (65.61±26.55) cm/s vs (64.82±27. 22) cm/s, RI (0.67±0. 082) vs (0. 68±0. 075), both P＞0.05].Conclusion: Our study indicated that HRT may has an effect to reduce the carotid IMT thickness, inhibit the plaque formation, and make the plaques harder and more stable. The long-term low-dose HRT may protect the postmenopausal women against the artherosclerosis of the carotid artery.
文摘The recent shift of the concept of cardiovascular disease as a chronic progressive condition,potentially involving multiple districts,has driven attention to the optimal management of patients with concomitant coronary and peripheral artery disease,representing a subset of patients with an increased risk of events and impaired survival.Recent pharmacological achievements in terms of antithrombotic therapy and lipid-lowering drugs allow multiple therapeutical combinations,thus requiring optimizing the treatment in a tailored fashion according to patients’risk profiles.Nevertheless,data dedicated to this specific subset of patients are still modest.We summarize currently available strategies and indications for the management of antithrombotic and lipid-lowering drugs in patients with the poly-vascular disease.
基金financially supported in the our laboratory with resources from The National Council of Technological and Scientific Developmentthe State of Sao Paulo Research Foundationthe National Institute of Science and Technology of Complex Fluids.
文摘For human immunodeficiency virus(HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy(HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.
文摘The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is an absolute requirement for lesion development. This allows us to consider intracellular cholesterol retention as a novel target for anti-atherosclerotic therapy. In this case, the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review summarizes the results of our basic studies shedding light on the mechanisms of intracellular cholesterol retention. We describe our cellular models to search for anti-atherosclerotic agents and demonstrate the use of these models for the development of anti-atherosclerotic drugs. We use natural products as the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy should be long-term or even lifelong. Using cellular models and natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured subendothelial aortic cells. We have developed drugs that reduce intracellular cholesterol retention, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinics. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.
文摘Coronary artery disease(CAD)is the leading cause of death worldwide,but because of several factors,one of which is antiplatelet therapy,the mortality rates have steadily declined.However,women continue to experience higher CAD mortality rates than men.This may be explained by differences in comorbidities,increased time to presentation,higher bleeding rates,and differences in management.There are numerous landmark trials in the field of antiplatelet therapy;however,women are consistently underrepresented in these trials.The results of these trials reveal that women experience the same benefit as men from antiplatelet therapy but experience higher bleeding rates;therefore bleeding-reduction strategies are imperative in this patient population.This review provides an overview of the available evidence on CAD in women and its implications for antiplatelet medications.
文摘Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular cholesterol retention is the principal event in the genesis of atherosclerotic lesions. This allows us to consider cellular retention of cholesterol as a novel target for anti-atherosclerotic therapy. In this case the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review describes our approach based on the use of cultured human arterial cells for the development of direct anti-atherosclerotic therapy. We use natural products as the basis of promising drugs for anti-atherosclerotic therapy. Using natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured cells. Our knowledge of the mechanisms of atherosclerosis is the foundation on which we have developed drugs that have a direct anti-atherosclerotic effect, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with allicor or inflaminat has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Karinat prevents the development of carotid atherosclerosis in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinical practice. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.
基金Supported by the Natural Science Foundation of Shaanxi,China(No.2004C2_51)
文摘Objective： To explore the efficacy of interventional therapy for chronic atherosclerotic occlusive disease of the lower extremity. Methods： Fifty-six cases of simple atherosclerotic occlusive disease of lower extremity were divided into 3 types according to the location of occhision, including 17 cases of abdominal aorta-iliac artery, 18 cases of iliac-femoral artery, and 21 cases of inferior popliteal artery. Catheter and guide wire combined with blunt dissection and subtle banding were used to dredge the occluded vessels, and stents were implanted when interlayer appeared. Results： After the treatment, 46 cases of occlusion were dredged （82.1%）, 6 cases remained occluded with the same symptoms （10.7%）, and 4 cases had severer symptoms （7.1%）. Among the 46 successful cases, there were 16 cases of abdominal aorta-iliac artery （94.1%）, 16 cases of iliac-femoral artery （88.9%） and 14 cases of inferior popliteal artery, artery （66.6%）. There was no statistical difference between the abdominal aorta-iliac artery cases and iliac-femoral artery cases （P〉0.05）, but there was statistical difference between these two types and the inferior popliteal artery cases （P〈0.05）. In the successful cases, 9 cases of abdominal aorta-iliac artery （52.9%）, 10 cases of iliac-femoral artery （55.5%） and 10 cases of inferior popliteal artery （33.3%） had 5-10 cm of occlusion, with no statistical difference between the first two types （P〉0.05）, but with statistical difference between the first two types and the third type （P〈0.05）. Compared with the 14 dredged cases （71.4%）, the 7 cases （33.3%） of inferior popliteal artery cases had richer compensatory circulation （P〈0.05）. Conclusion： It＇s safe and effective to treat simple atherosclerotic occlusive disease of the lower extremity with interventional therapy. The location and length of occlusion and the abundance of compensatory circulation had effect on the therapy.
