Aim Salidroside （SAL） is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density li...Aim Salidroside （SAL） is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density lipoprotein receptor - deficient mice. This study was to investigate the molecular mechanism of antiatherogenic effects of SAL. Method Six-week old apoE-/- male mice were fed a high-fat diet for 8 weeks and then were ad- ministered with SAL for another 8 weeks. Atherosclerotic lesion and vascular function were analyzed. Primary cul- tured human umbilical vein endothelial cells （HUVECs） were prepared. Superoxide anion （O2^-）, NO produc- tion, mitochondrial membrane potential （△ψm） and intracellular ATP and AMP levels were measured. Expression of eNOS and AMPK were analyzed by Western blot. Result SAL significantly improved endothelial function asso- ciated with increasing eNOS activation thus reduced the atherosclerotic lesion area. SAL increased eNOS-Serl177 phosphorylation and decreased eNOS-Thr495 phosphorylation. SAL significantly activated AMP-activated protein ki- nase （AMPK）. Both AMPK inhibitor and AMPK small interfering RNA （siRNA） abolished SAL-induced Akt- Ser473 and eNOS-Serl177 phosphorylation. In contrast, LY294002, the PI3k/Akt pathway inhibitor, abolished SAL-induced phosphorylation and expression of eNOS. SAL decreased cellular ATP content and increased the cel- lular AMP/ATP ratio, which was associated with the activation of AMPK. SAL was found to decrease A^m, which is likely consequence of reduced ATP production. Conclusion The action of SAL to reduce atherosclerotic lesion formation may at least be attributed to its effect on improving endothelial function by promoting nitric oxide （NO） production, which was associated with mitochondria depolarization and subsequent activation of the AMPK/PI3 IC/ Akt/eNOS pathway. Taken together, our data described the effects of SAL on mitochondria, which played critical roles in improving endothelial function in atherosclerosis.展开更多
Autoimmune rheumatic diseases (ARDs) have been closely associated with accelerated plaque progression and the development of atherosclerosis, which lead to high morbidity and mortality rates for cardiovascular disease...Autoimmune rheumatic diseases (ARDs) have been closely associated with accelerated plaque progression and the development of atherosclerosis, which lead to high morbidity and mortality rates for cardiovascular diseases. Endothelial dysfunction and arterial stiffness are greatly evidenced in several studies in the early phase of atherosclerosis. In ARDs, endothelial dysfunction and arterial stiffness are related to traditional and non-traditional risk factors. To date, no studies have clearly analyzed the main parameter involved in endothelial dysfunction and arterial stiffness. In this context, the present narrative review’s purpose was to describe the main factor in endothelial dysfunction and arterial stiffness in different ARDs. Endothelial dysfunction and arterial stiffness are related to traditional risk factors (i.e., hypertension, diabetes, dyslipidemia, metabolic syndrome, sedentary behavior) and non-traditional risk factors (linked to the immune mechanisms involved in these diseases). Moreover, in the present study, these associations were systemically analyzed in ankylosing spondylitis, antiphospholipid syndrome, rheumatoid arthritis, psoriatic arthritis, systemic autoimmune myopathies, systemic lupus erythematosus and systemic sclerosis. The present review shows that the relationship of traditional risk factors and non-traditional risk factors related to ARDs works in the worsening of function and structural properties of arterial vessels, leading to high cardiovascular morbidity and mortality.展开更多
BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus,but there is scarce data on hepatitis B virus infection.The hypothesis of this study is tha...BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus,but there is scarce data on hepatitis B virus infection.The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen(HBeAg)negative subjects.AIM To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.METHODS Prospective case-control collaborative study conducted in two tertiary hospitals.Four hundred and two subjects prospectively recruited at the outpatient clinic were included from May 2016 to April 2017:201 naïve HBeAg-negative hepatitis B virus-infected[49 chronic hepatitis B(CHB)and 152 inactive carriers(ICs)]and 201 healthy controls.Anthropomorphic and metabolic measures,liver stiffness and carotid Doppler ultrasound were performed.Subclinical atherosclerosis was established on an intima-media thickness increase of≥1.2 mm and/or the presence of carotid plaques.Normally distributed quantitative variables were compared with the Student t test and those with a non-normal distribution with the Mann-Whitney U test.Categorical variables were compared between groups using theχ2 or Fisher exact test.RESULTS Carotid plaques were found more often in CHB(32.7%)than ICs(17.1%)or controls(18.4%)(P=0.048).Subclinical atherosclerosis was also increased in CHB(40.8%)vsICs(19.1%)or controls(19.4%)(P=0.003).No differences in the risk of atherosclerosis were observed between controls and ICs.The factors independently associated with the presence of carotid plaques were age[odds ratio(OR)1.43,P<0.001]and CHB(OR 1.18,P=0.004)and for subclinical atherosclerosis,age(OR 1.45,P<0.001),CHB(OR 1.23,P<0.001)and diabetes(OR 1.13,P=0.028).In the subset of young subjects(<50 years),carotid plaques(12.5%vs 1.1%,P=0.027)and subclinical atherosclerosis(12.5%vs 2.2%,P=0.058)were more frequent among CHB than ICs.CONCLUSION Untreated HBeAg-negative CHB is an independent risk factor for carotid plaques and subclinical atherosclerosis,while ICs present a similar risk to controls.展开更多
Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis,while the underlying mechanism remains elusive.Here,we report that the non-canonical stimulator of interferon genes(STING)-...Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis,while the underlying mechanism remains elusive.Here,we report that the non-canonical stimulator of interferon genes(STING)-PKR-like ER kinase(PERK)pathway was significantly activated in both human and mice atherosclerotic arteries.Typically,STING activation leads to the activation of interferon regulatory factor 3(IRF3)and nuclear factor-kappa B(NF-κB)/p65,thereby facilitating IFN signals and infammation.In contrast,our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4(BRD4)expression,which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines,thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process.Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation.Mechanistically,this pathway is triggered by leaked mitochondrial DNA(mtDNA)via mitochondrial permeability transition pore(mPTP),formed by voltage-dependent anion channel 1(VDAC1)oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation.Especially,compared to macrophages,endothelial STING activation plays a more pronounced role in atherosclerosis.We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3,NF-κB and BRD4 in inflammatory responses,which provides emerging therapeutic modalities for vascular endothelial dysfunction.展开更多
Endothelial-to-mesenchymal transition(EndMT)is a key driver of atherosclerosis.Aerobic glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate levels.Histone lactylation,mediate...Endothelial-to-mesenchymal transition(EndMT)is a key driver of atherosclerosis.Aerobic glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate levels.Histone lactylation,mediated by lactate,can regulate gene expression and participate in disease regulation.However,whether histone lactylation is involved in atherosclerosis remains unknown.Here,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’arteries.Mechanistically,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting EndMT.We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction.Functional analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development.Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced atherosclerosis.This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.展开更多
Background Recent studies have suggested that Kawasaki disease(KD)may cause endothelial dysfunction,which can potentially induce atherosclerosis.However,there is still no consensus on the relationship between KD and a...Background Recent studies have suggested that Kawasaki disease(KD)may cause endothelial dysfunction,which can potentially induce atherosclerosis.However,there is still no consensus on the relationship between KD and atherosclerosis.This article aimed to determine whether patients with a history of KD may be at increased risk for accelerated atherosclerosis via a meta-analysis.Methods The PubMed,Embase,and SpringerLink databases were systematically searched.Studies on risk factors for ath-erosclerosis were included.A meta-analysis of case-control studies was performed using RevMan 5.3 software.Results Twenty studies were included with a total of 1684 subjects(990 patients after KD and 694 controls).The meta-analysis showed that the level of carotid intima media thickness(cIMT)(95%CI:0.01,0.03;P=0.005)and high-sensitivity C-reactive protein(hsCRP)(95%CI:0.00,0.10;P=0.03)were significantly higher in patients after KD than controls,whereas flow-mediated dilatation(FMD)(95%CI:-5.14,-1.26;P=0.001)in patients after KD was significantly lower.There were no significant differences in total cholesterol(TC)(95%CI:-0.13,5.92;P=0.06),low-density lipoprotein cholesterol(LDL)(95%CI:-0.65,2.08;P=0.31),or triglycerides(TG)(95%CI:-1.94,8.03;P=0.23).Conclusion Endothelial dysfunction and infammatory processes may exist in patients with a history of KD,which are risk factors for the development of atherosclerosis.展开更多
Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface ...Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface markers,which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development.This breakthrough stimulated research to understand the mechanism(s)underlying their physiologic function to allow development of new therapeutic options.One focus has been on their ability to form new vessels in injured tissues,and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels.Moreover,measures of their density have been shown to be a better predictor of cardiovascular events,both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification.In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies,in an attempt to better understand their function,which may lead to potential advancement in clinical management.展开更多
Objective:To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for ...Objective:To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis.Serum NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol.The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Results:Cholesterol diet significantly increased serum levels of cholesterol and LDL,caused a remarkable platelet hyperaggregability,and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination.The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclerosis. Conclusion:The present study suggests that the endothelial dysfunction caused by enhanced serum cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.展开更多
文摘Aim Salidroside （SAL） is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density lipoprotein receptor - deficient mice. This study was to investigate the molecular mechanism of antiatherogenic effects of SAL. Method Six-week old apoE-/- male mice were fed a high-fat diet for 8 weeks and then were ad- ministered with SAL for another 8 weeks. Atherosclerotic lesion and vascular function were analyzed. Primary cul- tured human umbilical vein endothelial cells （HUVECs） were prepared. Superoxide anion （O2^-）, NO produc- tion, mitochondrial membrane potential （△ψm） and intracellular ATP and AMP levels were measured. Expression of eNOS and AMPK were analyzed by Western blot. Result SAL significantly improved endothelial function asso- ciated with increasing eNOS activation thus reduced the atherosclerotic lesion area. SAL increased eNOS-Serl177 phosphorylation and decreased eNOS-Thr495 phosphorylation. SAL significantly activated AMP-activated protein ki- nase （AMPK）. Both AMPK inhibitor and AMPK small interfering RNA （siRNA） abolished SAL-induced Akt- Ser473 and eNOS-Serl177 phosphorylation. In contrast, LY294002, the PI3k/Akt pathway inhibitor, abolished SAL-induced phosphorylation and expression of eNOS. SAL decreased cellular ATP content and increased the cel- lular AMP/ATP ratio, which was associated with the activation of AMPK. SAL was found to decrease A^m, which is likely consequence of reduced ATP production. Conclusion The action of SAL to reduce atherosclerotic lesion formation may at least be attributed to its effect on improving endothelial function by promoting nitric oxide （NO） production, which was associated with mitochondria depolarization and subsequent activation of the AMPK/PI3 IC/ Akt/eNOS pathway. Taken together, our data described the effects of SAL on mitochondria, which played critical roles in improving endothelial function in atherosclerosis.
文摘Autoimmune rheumatic diseases (ARDs) have been closely associated with accelerated plaque progression and the development of atherosclerosis, which lead to high morbidity and mortality rates for cardiovascular diseases. Endothelial dysfunction and arterial stiffness are greatly evidenced in several studies in the early phase of atherosclerosis. In ARDs, endothelial dysfunction and arterial stiffness are related to traditional and non-traditional risk factors. To date, no studies have clearly analyzed the main parameter involved in endothelial dysfunction and arterial stiffness. In this context, the present narrative review’s purpose was to describe the main factor in endothelial dysfunction and arterial stiffness in different ARDs. Endothelial dysfunction and arterial stiffness are related to traditional risk factors (i.e., hypertension, diabetes, dyslipidemia, metabolic syndrome, sedentary behavior) and non-traditional risk factors (linked to the immune mechanisms involved in these diseases). Moreover, in the present study, these associations were systemically analyzed in ankylosing spondylitis, antiphospholipid syndrome, rheumatoid arthritis, psoriatic arthritis, systemic autoimmune myopathies, systemic lupus erythematosus and systemic sclerosis. The present review shows that the relationship of traditional risk factors and non-traditional risk factors related to ARDs works in the worsening of function and structural properties of arterial vessels, leading to high cardiovascular morbidity and mortality.
基金IV Fellowship Gilead-Research projects in HIV and hepatitisfunded by Gilead Science,No.GLD16_00057.
文摘BACKGROUND There is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus,but there is scarce data on hepatitis B virus infection.The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen(HBeAg)negative subjects.AIM To assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.METHODS Prospective case-control collaborative study conducted in two tertiary hospitals.Four hundred and two subjects prospectively recruited at the outpatient clinic were included from May 2016 to April 2017:201 naïve HBeAg-negative hepatitis B virus-infected[49 chronic hepatitis B(CHB)and 152 inactive carriers(ICs)]and 201 healthy controls.Anthropomorphic and metabolic measures,liver stiffness and carotid Doppler ultrasound were performed.Subclinical atherosclerosis was established on an intima-media thickness increase of≥1.2 mm and/or the presence of carotid plaques.Normally distributed quantitative variables were compared with the Student t test and those with a non-normal distribution with the Mann-Whitney U test.Categorical variables were compared between groups using theχ2 or Fisher exact test.RESULTS Carotid plaques were found more often in CHB(32.7%)than ICs(17.1%)or controls(18.4%)(P=0.048).Subclinical atherosclerosis was also increased in CHB(40.8%)vsICs(19.1%)or controls(19.4%)(P=0.003).No differences in the risk of atherosclerosis were observed between controls and ICs.The factors independently associated with the presence of carotid plaques were age[odds ratio(OR)1.43,P<0.001]and CHB(OR 1.18,P=0.004)and for subclinical atherosclerosis,age(OR 1.45,P<0.001),CHB(OR 1.23,P<0.001)and diabetes(OR 1.13,P=0.028).In the subset of young subjects(<50 years),carotid plaques(12.5%vs 1.1%,P=0.027)and subclinical atherosclerosis(12.5%vs 2.2%,P=0.058)were more frequent among CHB than ICs.CONCLUSION Untreated HBeAg-negative CHB is an independent risk factor for carotid plaques and subclinical atherosclerosis,while ICs present a similar risk to controls.
基金supported by the National Nature Science Foundation of China(82270421,81970428,31771334,81800385,82270484,81873654,31800971,and 82170503)the Major Research Plan of the National Natural Science Foundation of China(91649125)+5 种基金University Natural Science Research of Jiangsu Province(18KJB310008,China)Natural Science Foundation of Jiangsu Province(BK20180684,China)supported by the program of special professor of Jiangsu Provincethe program of the special medical experts of Jiangsu Provincethe program of innovation and entrepreneurship team plan of Jiangsu ProvinceMajor project supported by the Basic Science(Natural Science)Foundation of the Jiangsu Higher Education Institutions,Jiangsu Provincial Social Development Project(BE2021749,China).
文摘Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis,while the underlying mechanism remains elusive.Here,we report that the non-canonical stimulator of interferon genes(STING)-PKR-like ER kinase(PERK)pathway was significantly activated in both human and mice atherosclerotic arteries.Typically,STING activation leads to the activation of interferon regulatory factor 3(IRF3)and nuclear factor-kappa B(NF-κB)/p65,thereby facilitating IFN signals and infammation.In contrast,our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4(BRD4)expression,which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines,thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process.Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation.Mechanistically,this pathway is triggered by leaked mitochondrial DNA(mtDNA)via mitochondrial permeability transition pore(mPTP),formed by voltage-dependent anion channel 1(VDAC1)oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation.Especially,compared to macrophages,endothelial STING activation plays a more pronounced role in atherosclerosis.We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3,NF-κB and BRD4 in inflammatory responses,which provides emerging therapeutic modalities for vascular endothelial dysfunction.
基金supported by the National Natural Science Foundation of China(82270421,81970428,31771334,81800385,82270484,82370376,82121001,82030013,and 82241211)Major Research Plan of the National Natural Science Foundation of China(91649125)+3 种基金the National Key R&D Program of China(2019YFA0802704)The major project of Natural Science Foundation of the Jiangsu Higher Education Institution of China(21KJA310006)Jiangsu Provincial Social Development Project(BE2021749,China)Special Program for Top Innovative Talents(NJMUTY20230082,China).
文摘Endothelial-to-mesenchymal transition(EndMT)is a key driver of atherosclerosis.Aerobic glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate levels.Histone lactylation,mediated by lactate,can regulate gene expression and participate in disease regulation.However,whether histone lactylation is involved in atherosclerosis remains unknown.Here,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’arteries.Mechanistically,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting EndMT.We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction.Functional analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development.Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced atherosclerosis.This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.
基金This research was supported by the Specially Appointed Medical Expert Project of Jiangsu Commission of Health(2019)the Medical Science and Technique Foundation of Nanjing Health Commission(YKK19104).
文摘Background Recent studies have suggested that Kawasaki disease(KD)may cause endothelial dysfunction,which can potentially induce atherosclerosis.However,there is still no consensus on the relationship between KD and atherosclerosis.This article aimed to determine whether patients with a history of KD may be at increased risk for accelerated atherosclerosis via a meta-analysis.Methods The PubMed,Embase,and SpringerLink databases were systematically searched.Studies on risk factors for ath-erosclerosis were included.A meta-analysis of case-control studies was performed using RevMan 5.3 software.Results Twenty studies were included with a total of 1684 subjects(990 patients after KD and 694 controls).The meta-analysis showed that the level of carotid intima media thickness(cIMT)(95%CI:0.01,0.03;P=0.005)and high-sensitivity C-reactive protein(hsCRP)(95%CI:0.00,0.10;P=0.03)were significantly higher in patients after KD than controls,whereas flow-mediated dilatation(FMD)(95%CI:-5.14,-1.26;P=0.001)in patients after KD was significantly lower.There were no significant differences in total cholesterol(TC)(95%CI:-0.13,5.92;P=0.06),low-density lipoprotein cholesterol(LDL)(95%CI:-0.65,2.08;P=0.31),or triglycerides(TG)(95%CI:-1.94,8.03;P=0.23).Conclusion Endothelial dysfunction and infammatory processes may exist in patients with a history of KD,which are risk factors for the development of atherosclerosis.
基金Supported by Grants from American Heart Association grant-in-aid,No.0455435BAmerican Heart Association SDG,No. 110350047ANIH Grant No.RO1-HL077566 and No.RO1-HL085119 to Zhang C
文摘Endothelial progenitor cells(EPCs)are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans.They express both hematopoietic and endothelial surface markers,which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development.This breakthrough stimulated research to understand the mechanism(s)underlying their physiologic function to allow development of new therapeutic options.One focus has been on their ability to form new vessels in injured tissues,and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels.Moreover,measures of their density have been shown to be a better predictor of cardiovascular events,both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification.In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies,in an attempt to better understand their function,which may lead to potential advancement in clinical management.
文摘Objective:To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis.Serum NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol.The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Results:Cholesterol diet significantly increased serum levels of cholesterol and LDL,caused a remarkable platelet hyperaggregability,and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination.The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclerosis. Conclusion:The present study suggests that the endothelial dysfunction caused by enhanced serum cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.
