稳定性冠心病患者循环内皮祖细胞与冠状动脉病变严重程度的分析

目的观察稳定性冠心病患者循环内皮祖细胞(EPCs)数量与冠状动脉病变严重程度的关系。方法对80例冠状动脉造影患者(排除急性冠状动脉综合征、心肌梗死)作病变严重程度及危险因素分析;以CD133/KDR作为EPCs标记物,用流式细胞仪检测患者的CD133/KDR双标记细胞数量。结果外周血EPCs数量与年龄、血清肌酐清除率(Ccr)、左室心肌重量指数(LVMI)呈负相关(P值分别=0.004,0.015,0.014);冠心病伴高血压患者较不伴高血压者EPCs数量显著减少(P=0.004)。冠状动脉造影阳性者EPCs数量较阴性者显著降低(P<0.01);EPCs数量与Gensini评分呈负相关(n=49,r=-0.305,P=0.039)。结论在稳定性冠心病患者循环EPCs数量与心血管危险因素及冠状动脉病变相关。     

冠心病患者循环内皮祖细胞与一氧化氮的关系及临床意义

目的探讨冠心病患者循环内皮祖细胞(EPCs)与NO的关系及临床意义。方法78例入选对象均经选择性冠状动脉造影明确有无冠状动脉狭窄,将其分为冠心病组42例,对照组36例。采集入选者外周血测定NO浓度,同时进行循环EPCs分离培养,14天后显微镜下计数细胞克隆形成单位评估循环EPCs水平。结果冠心病组NO水平明显低于对照组(P<0.001),双支、3支冠状动脉病变组较单支病变组NO水平明显降低(P<0.001)。冠心病组循环EPCs水平均明显低于对照组(P<0.01)。NO浓度与循环EPCs水平呈明显正相关(r=0.867,P<0.0001)。结论NO可能在EPCs动员、归巢过程中发挥重要作用,与冠心病发生及临床表现相关。     

冠心病患者循环内皮祖细胞与尿酸检测及相关性

目的探讨冠心病患者循环内皮祖细胞与尿酸的关系及临床意义。方法42例冠心病患者均经选择性冠状动脉造影证实有明显的冠状动脉狭窄;36例对照组经临床检查和选择性冠状动脉造影排除冠心病。测定各组患者血清尿酸水平;采集研究对象外周血进行内皮祖细胞的分离培养,14天后倒置相差显微镜下计数细胞克隆形成单位评估循环内皮祖细胞水平。结果冠心病组血清尿酸水平明显高于对照组(P<0.01),单支与多支冠状动脉病变组尿酸水平差异无显著性(P>0.05)。冠心病组中稳定型心绞痛组及急性冠状动脉综合征组循环内皮祖细胞水平均明显低于对照组(P<0.01);单支、双支、三支冠状动脉病变组内皮祖细胞水平均显著低于对照组(P<0.01)。血清尿酸与循环内皮祖细胞水平呈负相关(r=-0.382,P=0.037)。结论冠心病患者血清尿酸水平与循环内皮祖细胞水平呈负相关,血清尿酸可能通过抑制内皮祖细胞数量从而减弱内皮祖细胞参与损伤内皮修复的能力,与冠心病发生及临床表现相关。     

急性冠脉综合征患者危险因素与冠状动脉病变的相关性研究

目的探讨急性冠脉综合征(ACS)的危险因素与冠状动脉病变程度的相关性研究。方法回顾性分析我院疑诊ACS并行选择性冠状动脉造影检查(CAG)734例患者的临床资料,依据CAG结果将其分为非ACS组(129例)和ACS组(605例),分析冠心病危险因素与冠状动脉病变的关系,采用多因素Logistic回归分析筛选冠心病独立相关危险因素。结果 ACS组和非ACS组年龄、男性比例、高血压病、糖尿病、吸烟史、家族史者比例及高敏C反应蛋白(hs-CRP)水平比较差异有统计学意义(P<0.05);ACS组随着糖尿病、家族史等单个危险因素及年龄、男性比例、低密度脂蛋白胆固醇(LDL-C)水平的增加,冠状动脉病变支数、狭窄程度逐渐增加,差异有统计学意义(P<0.05),呈正相关;BMI、hs-CRP、UA、TC、TG、HDL-C、吸烟与冠状动脉病变支数、狭窄程度差别无统计学意义(P>0.05)。结论 hs-CRP、年龄、男性、糖尿病、高血压病、吸烟为冠心病的显著独立危险因素。     

非对性性二甲基精氨酸及循环内皮祖细胞与冠状动脉病变程度的相关性

目的 探讨冠心病患者非对称性二甲基精氨酸（ADMA）及循环内皮祖细胞（EPC）与冠状动脉病变程度的相关性。方法 80例冠心病患者均经选择性冠状动脉造影证实有明显的冠状动脉狭窄；50例对照者经选择性冠状动脉造影排除冠状动脉狭窄。根据病变程度分组，测定各组患者血浆ADMA水平；采集研究对象外周血进行EPC的分离培养；7～10天后倒置相差显微镜下计数细胞克隆形成单位（CFU）评估循环EPC数量。结果 冠心病单支及多支病变组血浆ADMA水平明显高于对照组（P<0.05和P<0.01），且多支病变组较单支病变组ADMA水平增高（P<0.05）；冠状动脉病变Gensini积分≥60分组、31～59分组和≤30分组血浆ADMA水平均明显高于对照组；随着Gensini积分及病变支数的增加，血浆ADMA水平明显上升（P<0.05和P<0.01）。冠心病组中单支及多支病变组循环EPC数量明显低于对照组（P<0.05和P<0.01）；冠状动脉病变Gensini积分三个分组中循环EPC数量明显低于对照组（P<0.01）。随着Gensini积分及病变支数的增加，EPC数量明显下降（P<0.05和P<0.01）。冠状动脉病变Gensini积分与血浆ADMA水平呈正相关（r0.365，P0.027），与循环EPC数量呈负相关（r－0.16，P0.015）；血浆ADMA水平与循环EPC数量呈负相关（P<0.01）。结论 随着冠状动脉病变程度的增加，体内ADMA水平逐渐增加，而EPC数量逐渐减少，冠心病的发生与ADMA的蓄积及EPC的减少相关。体内实验进一步证实ADMA可能通过抑制EPC的功能影响内皮再生化。     

青年冠心病临床分析

目的 探讨青年冠心病患者的心血管危险因素、冠状动脉病变特点与老年冠心病患者的不同点。方法 对56例青年(≤45岁)冠心病患者和66例老年(>60岁)冠心病患者的临床资料(包括冠状动脉造影结果)进行回顾性分析和比较。结果 青年冠心病组吸烟、大量饮酒、肥胖、心血管病家族史明显多于老年组(P<0.001或P<0.01),男性患者多(P=0.008),甘油三酯高(P=0.001)。老年冠心病组糖尿病多(P=0.034),心血管并发症多。青年组多冠状动脉单支病变(P<0.001),老年组多冠状动脉多支病变(P<0.00]),侧支循环多见于老年组。结论 吸烟、大量饮酒、肥胖、心血管病家族史是青年冠心病患者突出的危险因素,不良的生活饮食习惯和遗传因素促使冠心病提早发生。寻求新的无创检查方法筛选青年冠心病的高危人群,做好预防工作,有利于避免或延迟冠心病的发生。     

CD14+-内皮祖细胞数量与冠心病及心血管危险因素无关

目的:证据显示内皮祖细胞(EPCs)含两亚群即CD34+-EPCs和CD14+-EPCs.之前评估EPCs与冠心病关系的研究并没有区分CD34+-EPCs和CD14+-EPC8这两类细胞或只纳入了CD34+-EPCs.因此本研究探索了CD14+-EPCs数量与冠心病及心血管危险因素的关系.方法:100例患者入选(对照组34例,稳定性冠心病组41例,急性冠脉综合征组25例),CD14+-EPCs定义为表面标记CD14阳性和血管内皮生长因子受体-2(KDR)阳性细胞,用流式细胞仪检测其数量.结果:3组间CD14+-EPCs水平差异无统计学意义;CD14+-EPCs数量与冠状动脉严重程度或危险因素也无关.结论:CD14+-EPCs水平与冠心病严重程度或心血管危险因素无关.     

氯沙坦对冠心病外周血内皮祖细胞的动员作用及影响内皮功能的机制

目的观察氯沙坦对冠心病患者外周血内皮祖细胞(EPCs)数量及血流介导的内皮舒张功能的影响,并探讨其改善内皮功能的机制。方法选取经冠脉造影确诊为冠心病65例,随机分为标准治疗组32例和ARB治疗组33例,同时选取非冠心病31例作为健康对照组。标准治疗组给予常规药物,ARB治疗组给予常规物药+氯沙坦治疗,随访8周,治疗前后分别用流式细胞术检测EPCs水平、超声测定流量介导血管扩张(FMD)情况。结果基线水平,冠心病内皮功能较健康对照组明显低下、EPCs数量明显减少(P<0.05);FMD与EPCs数量呈正相关(r=0.57,P<0.01)。治疗8周后,标准治疗组和ARB治疗组冠心病患者FMD均有不同程度的改善,循环血EPCs数量均有不同程度的增加,但是ARB治疗组变化更明显(P<0.05);ARB治疗组EPCs的增加与内皮功能的改善呈正相关(r=0.52,P<0.01)。结论氯沙坦对EPCs具有一定的动员作用,ARB类药物氯沙坦可能通过增加外周血EPCs数量,进而改善内皮功能。     

老年人血浆胆红素水平与冠状动脉病变的关系

目的探讨老年人胆红素水平与冠状动脉病变的关系。方法选择疑似冠心病的老年患者132例,根据冠状动脉造影结果分为冠心病组(93例)和对照组(39例),对冠状动脉病变严重程度进行评分,并测定空腹血浆总胆红素、直接胆红素、间接胆红素水平。分析影响冠状动脉病变的相关因素及冠状动脉病变程度与胆红素的关系。结果与对照组比较,冠心病组患者总胆红素和间接胆红素水平明显降低,差异有统计学意义(P<0.05),两组直接胆红素水平比较,差异无统计学意义(P>0.05)。男性、年龄、空腹血糖、高血压和心肌梗死与冠状动脉病变严重程度呈正相关,总胆红素和间接胆红素水平与冠状动脉病变严重程度呈负相关。结论血浆胆红素水平与老年人冠状动脉病变的严重程度呈负相关,其中间接胆红素可能起着更重要的作用。     

多种危险因素与冠状动脉病变程度的相关性

目的探讨冠心病多种危险因素与冠状动脉病变程度的相关性。方法 157例患者依据冠状动脉造影结果分为冠心病组(102例)、对照组(55例)。研究同型半胱氨酸(HCY)、纤维蛋白原(FIB)、空腹血糖(GLU)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、血尿酸(UA)与冠状动脉病变程度的相关性。结果冠心病组与对照组比较,HCY、FIB、GLU、TC、LDL-C均有统计学差异(P0.05),UA无统计学差异(P0.05)。冠心病患者的HCY、FIB、GLU、TCH、LDL-C与冠状动脉病变程度之间呈显著相关性(P0.05),血尿酸与冠状动脉病变程度无相关性(P0.05)。结论对患者HCY、FIB、GLU、TCH、LDL-C水平进行监测及控制具有重要的临床意义,对于预防冠心病有积极的作用。     

Functional impairment of hematopoietic progenitor cells in patients with coronary heart disease

The circulating form of endothelial progenitors cells (EPCs) are derived from bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization of EPCs was shown to be linked to cardiac diseases. This study investigated whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number and functional properties of EPCs were assessed in 15 healthy controls, and 40 patients with CHD. The colony-forming unit (CFU) capacity of BM-derived mononuclear cells and the CD34+ HSC number were examined in four healthy volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01 vs. controls). Moreover, the migratory capacity was significantly impaired in EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was an independent predictor of functional EPC impairment. CFUs were reduced in CHD patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also predictor of impaired CFU capacity. In this small clinical study, CHD is associated with selective impairment of HSC function in the BM and in the peripheral blood, which may contribute to impairment of cardiac function.     

冠心病患者介入治疗前后循环内皮祖细胞数量的变化

目的 观察并比较正常人与不同类型冠心病患者外周血中内皮祖细胞(EPCs)数量的差异,以及不同类型冠心病患者在经皮冠状动脉介入治疗(PCI)前后外周血中EPCs的数量变化.方法 将患者分成4组:稳定性心绞痛组、不稳定性心绞痛组、急性ST段抬高型心肌梗死组及正常对照组.利用流式细胞术双色分析法检测对照组以及3组不同类型冠心病患者在PCI术前、术后即刻、术后24 h EPCs占外周血有核细胞的百分比,其中EPCs以CD133~+/VEGFR-2~+双标记阳性确定.结果 PCI术前,外周血中EPCs数量在稳定性心绞痛组为(0.043±0.043)%、不稳定性心绞痛组为(0.014±0.018)%、急性ST段抬高型心肌梗死组为(0.040±0.036)%,均明显低于正常对照组[(0.111%±0.078)%](均P＜0.01),不稳定性心绞痛组外周血中EPCs的数量明显低于稳定性心绞痛组(P＜0.05).不稳定性心绞痛组外周血中EPCs的数量在PCI术后24 h较术前明显增加[(0.054±0.045)%比(0.014±0.018)%,P＜0.01].稳定性心绞痛组及急性ST段抬高型心肌梗死组PCI术前、术后EPCs的数量差异无统计学意义.结论 外周血中EPCs数量的变化可能与冠心病的病变程度有关.PCI对外周血EPCs数量的影响可能与冠心病类型有关.     

血清Lp-PLA2 GGT与冠心病及冠状动脉病变严重程度的相关性分析

目的分析血清脂蛋白相关磷脂酶A2(Lp-PLA2)、γ-谷氨酰转移酶(GGT)与冠心病(CHD)及冠状动脉病变严重程度的相关性。方法选择2018-06~2019-06于郑州大学第二附属医院心内科首次就诊的170例疑似CHD患者的临床资料,根据冠状动脉造影检查结果分为CHD组(103例)和非CHD组(67例)。检测患者血清Lp-PLA2、GGT水平,分析血清Lp-PLA2、GGT与CHD及冠状动脉病变严重程度的关系。结果CHD组Lp-PLA2、GGT、甘油三酯(TG)、低密度脂蛋白(LDL)、Gensin积分水平以及合并高血压、糖尿病人数比例显著高于非CHD组(P<0.05),而高密度脂蛋白(HDL)水平显著低于非CHD组(P<0.05)。Spearman相关分析结果显示,CHD患者血清Lp-PLA2、GGT水平与冠状动脉病变支数呈正相关(rs=0.681,P=0.000;rs=0.603,P=0.000)。Pearson相关分析结果显示,CHD患者血清Lp-PLA2、GGT水平与Gensin积分呈正相关(r=0.799,P=0.000;r=0.621,P=0.000)。多因素logistic分析结果显示,较高水平的Lp-PLA₂、GGT和LDL,以及合并高血压是促进CHD发生的危险因素(P<0.05);而较高水平的HDL是抑制CHD发生的保护因素(P<0.05)。结论较高水平的血清Lp-PLA2、GGT是促进CHD发生的危险因素,可较好地反映冠状动脉病变严重程度,可作为评估CHD发生、进展的可靠指标。     

冠心病患者胰岛素水平与内皮祖细胞及冠状动脉病变的相关性

目的 探讨冠心病患者不同胰岛素水平与循环内皮祖细胞(EPC)数量、功能及冠状动脉病变程度的关系并探讨相关临床意义.方法 69例经选择性冠状动脉造影证实的冠心病患者,按胰岛素水平高低分为胰岛素抵抗(IR)组和胰岛素敏感(IS)组,另设25例健康对照者.采集研究对象外周血以激酶插入区域受体(KDR)和CD133双阳性为循环EPC标记行流式细胞分析,同时采血进行EPC的分离培养,7 d后鉴定并检测增殖及迁移能力,将各组的一般临床资料,循环EPC数量、迁移、增殖能力指标、稳态模型胰岛素抵抗指数(HOMA-IR)及冠状动脉病变Gensini评分进行统计学分析.结果 IR组循环EPC数量明显少于IS组[(0.34±0.08)‰比(0.47±0.09)‰,P<0.01],HOMA-IR自然对数与循环EPC数量呈负相关(r=-0.291,P=0.01),循环EPC数量与Gensini评分呈负相关(r=-0.3984,P=0.006).IR组的增殖能力和迁移能力均低于IS组减弱(P<0.05).结论 冠心病患者血清胰岛素水平与循环EPC数量呈负相关.循环EPC数量及功能与冠状动脉病变程度呈负相关;IR或高胰岛素血症可能部分通过损害循环EPC的数量及功能,从而影响冠状动脉病变程度.     

冠心病患者内皮祖细胞与动脉弹性相关性及缬沙坦干预研究

目的探讨冠状动脉粥样硬化性心脏病(coronary heart disease,CHD)患者内皮祖细胞(endothelial progenitor cell,EPCs)数量及动脉弹性指数之间的相关性,以及缬沙坦干预后EPCs水平和动脉弹性指数变化。方法冠状动脉造影检查确诊的冠心病患者60例为CHD组,同期排除冠心病的门诊健康体检者60例为对照组。两组患者采集外周血用密度梯度离心法获取单个核细胞,接种在人纤维连接蛋白包被的培养板,培养贴壁后进行细胞化学分析。激光共聚焦显微镜鉴定FITC-UEA-I和DiI-acLDL双染色阳性细胞为正在分化的EPC。进行EPCs水平测定。动脉弹性功能检测仪测定患者的大、小动脉弹性指数(C1、C2)。CHD组患者术后缬沙坦80mg/天干预12、24周后再次检测EPCs水平和动脉弹性指数。结果CHD组EPCs数量、C1、C2分别为32.8±6.4 EPCs/×200视野、9.82±1.54、3.67±0.87,对照组为61.6±9.5 EPCs/×200视野、15.3±2.52、7.51±2.03,两组差异有显著统计学意义(P<0.01);CHD组动脉弹性功能指数与EPCs水平呈正相关(r值分别为0.94、0.98,均P<0.01)。CHD组患者缬沙坦80mg/天干预12、24周后EPCs数量明显增加(37.7±7.98 vs 50.80±8.10,P<0.01),动脉弹性指数改善(C1:10.6±1.98 vs 12.55±2.43,C2:4.37±1.03 vs 5.77±1.99,均P<0.01),差异有显著统计学意义。结论CHD患者EPCs水平减低和动脉弹性指数下降是冠心病发病的独立危险因素之一,且两者之间呈正相关。CHD患者缬沙坦80mg/天干预12、24周后明显提高EPCs数量和动脉弹性指数。     

Evidence for genetic regulation of endothelial progenitor cells and their role as biological markers of atherosclerotic susceptibility.

AIMS: Endothelial progenitor cells (EPCs) are found in the peripheral circulation and are capable of endothelial repair and neovascularization. EPC number and function are reduced in subjects with cardiovascular risk factors or proven coronary artery disease (CAD). We hypothesized that EPC number and/or function may be genetically regulated and may vary in healthy adult offspring depending on parental history of CAD. METHODS AND RESULTS: We studied 102 subjects comprising 24 healthy parent-healthy offspring pairs and 27 CAD parent-healthy offspring pairs. We measured the number of circulating CD34(+)VEGFR-2(+) and AC133(+)VEGFR-2(+) EPCs, the number of EPCs grown in culture, and the migration capacity of cultured EPCs towards vascular endothelial growth factor. There was significant correlation in the number of cultured EPCs between healthy parents and their offspring (R = 0.492, P = 0.015) and CAD parents and their offspring (R = 0.751, P < 0.001). Offspring of subjects with CAD had significantly higher numbers of circulating CD34(+)VEGFR-2(+) and AC133(+)VEGFR-2(+) cells (P = 0.018 and P < 0.001, respectively). There was no difference in migration capacity between groups. CONCLUSION: Our results suggest that EPC number is, at least in part, genetically regulated. Circulating EPCs may represent biological markers of occult vascular damage in offspring with hereditary risk of CAD.     

Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation.

BACKGROUND: Endothelial progenitor cells (EPC) are present in peripheral blood and can develop a functional endothelial phenotype. The number and function of circulating EPCs are altered in atherosclerosis, diabetes, and after myocardial infarction and EPCs have been shown to promote postnatal angiogenesis and vasculogenesis. We investigated the number and adhesive properties of EPCs from patients with unstable angina and no evidence of cardiac necrosis. METHODS AND RESULTS: Patients were selected with unstable angina (n=29) and no evidence of cardiac necrosis, and controls with stable angina (n=12) and atherosclerotic risk factors, medication use, and coronary vessel involvement similar to patients. Circulating EPC numbers were determined by colony-forming unit assay and their adhesive properties were evaluated by EPC capacity to bind immobilised fibronectin. High-sensitivity C-reactive protein (hsCRP) was determined in all patients. Circulating EPCs were significantly increased in patients with unstable as compared with stable angina (24.5+/-2.6 vs. 13.3+/-2.9, respectively). Seven unstable angina patients followed up for 3 months after clinical stabilisation exhibited a reduction of close to 50% in circulating EPC numbers. The adhesive capacity of EPCs from patients with unstable and stable angina did not differ. A positive correlation was found between systemic CRP levels and circulating EPC numbers, but not their adhesive capacity. CONCLUSION: Patients with unstable angina and no evidence of cardiac necrosis exhibited increased circulating EPCs. Systemic inflammation, in addition to recognised growth factors, could play a role in the peripheral mobilisation of EPCs in patients with anginal syndromes.     

The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease.

OBJECTIVES: The objective of this study was to determine whether the number of endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs) in peripheral blood was associated with the presence and severity of coronary artery disease (CAD) in patients undergoing coronary angiography. BACKGROUND: Previous studies have suggested an inverse relationship between levels of circulating EPCs/CACs and the presence of CAD or cardiovascular risk factors, whereas other studies have observed increased numbers of EPCs in the setting of acute ischemia. However, the criteria used to identify specific angiogenic cell subpopulations and methods of evaluating CAD varied in these studies. In the present study, we used rigorous criteria to identify EPCs and CACs in the blood of patients undergoing coronary angiography. METHODS: The number of EPCs and CACs were measured in the blood of 48 patients undergoing coronary angiography. Patients with acute coronary syndromes were excluded. RESULTS: Compared with patients without angiographically significant CAD, the number of EPCs was increased (1.11 +/- 2.50 vs. 4.01 +/- 3.70 colonies/well, p = 0.004) and the number of CACs trended higher (175 +/- 137 vs. 250 +/- 160 cells per mm(2), p = 0.09) among patients with significant CAD. The highest levels of EPCs were isolated from patients subsequently selected for revascularization (5.03 +/- 4.10 colonies/well). CONCLUSIONS: In patients referred for coronary angiography, higher numbers of EPCs, and a trend toward higher numbers of CACs, were associated with the presence of significant CAD, and EPC number correlated with maximum angiographic stenosis severity. Endothelial progenitor cell levels were highest in patients with CAD selected for revascularization.