血管内皮祖细胞与冠心病危险因素相关性研究进展

血管内皮祖细胞不仅参与胚胎期血管的生成,而且也参与出生后血管的修复、再生及肿瘤的生长等过程。近几年的研究表明内皮祖细胞与冠心病危险因素负性相关,同时提示了内皮祖细胞在动脉粥样硬化和冠心病的发生、发展中扮演的重要角色。     

同型半胱氨酸对冠心病外周血内皮祖细胞的研究现状

同型半胱氨酸作为动脉粥样硬化的一个独立危险因素,影响冠心病外周血内皮祖细胞的数量和功能,导致内皮功能障碍。本文就高同型半胱氨酸血症对内皮祖细胞的影响及作用机制的研究进展进行了综述。     

他汀类药物与内皮祖细胞

内皮祖细胞是来源于骨髓可分化为内皮细胞的一群细胞,在组织缺血及血管损伤时动员入血,参与微血管的生成及血管内皮的修复。有研究表明循环内皮祖细胞的数量和功能与冠心病危险因子呈负相关,提示循环内皮祖细胞有作为心血管疾病预后评估工具的应用前景。他汀类药物除了调节血脂的作用外,在血脂正常的动物模型中也发现能增加内皮祖细胞数量及增强内皮祖细胞功能,他汀类药物的这种作用可能是其临床上治疗冠心病获益的机制之一。     

未来治疗的新领域——内皮祖细胞

内皮祖细胞来源于骨髓,可分化为成熟有功能的内皮细胞.大量试验证实冠心病和心力衰竭患者内皮祖细胞数量减低,外周循环内皮祖细胞功能受损,许多因素可影响内皮祖细胞的数量及功能.因此,药物动员内皮祖细胞或使其功能正常化有望改善心血管病患者的预后.现总结近来关于影响内皮祖细胞因素的研究,有助于探索未来治疗的新领域.     

内皮祖细胞移植治疗冠心病研究进展

内皮细胞的损伤及功能障碍是促进冠心痛发生发展的首要因素,内皮祖细胞能够定向分化为成熟的内皮细胞,促进内皮修复和血管新生,因此为冠心病治疗提供了新的思路,现就内皮祖细胞移植在冠心病治疗方面的应用作一综述。     

内皮祖细胞在动脉粥样硬化进程中的作用

内皮祖细胞因参与再内皮化和血管新生,在动脉粥样硬化病变发生发展中可能起着举足轻重的作用,包括参与内皮损伤后修复与内膜增生,影响斑块发展与稳定以及对动脉粥样硬化性疾病严重程度的预测。动脉粥样硬化病变过程中若干危险因素影响了内皮祖细胞的数量和功能,从而削弱内皮祖细胞可能的血管保护作用并影响动脉粥样硬化进程,因而提出内皮祖细胞潜在的治疗作用。本文从再内皮化、斑块发展和血管新生、动脉粥样硬化的若干危险因素及内皮祖细胞的预测价值和治疗作用等方面对内皮祖细胞在动脉粥样硬化进程中的作用作一综述。     

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。     

内皮祖细胞与冠心病

内皮祖细胞是内皮细胞的前体细胞,近年研究表明它在冠心病的发生、发展中扮演了重要角色。本文就冠心病患者内皮祖细胞数量、功能的改变及内皮祖细胞在冠心病的治疗应用等方面研究进展作一综述。     

内皮祖细胞与脑动脉粥样硬化的相关性研究

目的探讨内皮功能紊乱的标志物(内皮祖细胞)与脑动脉粥样硬化的相关性。方法对131例患者采用流式细胞术检测外周血内皮祖细胞数量及(DSA)评估颅内外脑动脉粥样硬化程度。记录人口统计学资料和血管危险因素,并进行比较分析。结果控制混杂因素后,与对照组相比发生脑动脉粥样硬化组的内皮祖细胞水平显著降低(OR=0.344;95%CI,0.150~0.792;P=0.012),其次,多元Logistic回归分析显示,内皮祖细胞计数与脑动脉粥样硬化的部位呈负相关。颅内动脉粥样硬化与内皮祖细胞计数无统计学意义(P0.05)。结论内皮祖细胞是脑动脉粥样硬化的较好独立预测因素,内皮祖细胞数量降低与脑动脉粥样硬化存在潜在的病理生理联系。     

内皮祖细胞在动脉粥样硬化过程中所起作用的研究进展

动脉粥样硬化性疾病的发病率和病死率很高。以往的观点认为,内皮损伤引发炎症反应,导致动脉粥样硬化性病变。如今对于动脉粥样硬化的研究已经不局限于血管壁受损,它与内皮祖细胞的改变也存在很大的相关性。现就影响内皮祖细胞的危险因素,到内皮祖细胞减少及功能障碍的机制,再到斑块的形成,最后到临床症状的出现,综述了内皮祖细胞在动脉粥样硬化形成、发展过程中所起的作用。     

循环EPCs CD34^＋水平与高血压病患者心血管危险因素的关系

目的探讨能否将循环内皮祖细胞(EPCs)CD34 水平作为评价高血压病患者心血管危险度的标志。方法高血压病患者组62例,对照组20例。高血压病患者采用Framingham心血管危险因素积分分层心血管危险因素,分为低危组18例,中危组14例,高危组17例,极高危组13例。作外周血循环EPCs CD34 水平与Framingham心血管危险因素积分的相关性分析。结果各研究组高血压病患者外周循环EPCs CD34 水平随着其心血管危险程度的增加,逐步下降,各组间比较有统计学意义(P<0.05)。EPCs CD34 水平与Framingham心血管危险因素积分呈负相关关系(r=-0.875,P<0.01)。结论高血压病患者循环EPCs CD34 水平下降与心血管危险因素有显著的相关性。循环EPCs CD34 水平可以作为高血压病患者心血管危险度的标志。     

血管内皮祖细胞与冠状动脉硬化性心脏病危险因素的研究现状

内皮祖细胞是血管内皮细胞的前体,它不仅参与胚胎时期的血管生成,而且对出生后微血管新生、损伤血管内皮修复和功能维持中仍然有重要的作用。新近研究表明,内皮祖细胞与冠状动脉硬化性心脏病密切相关,与冠状动脉硬化性心脏病危险因素呈反向线形关系。本文就其与炎症因子、高同型半胱氨酸、血管紧张素Ⅱ、尿酸作一综述。     

Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy?

The ideal way to prevent and cure atherosclerosis and the subsequent end organ damage is to restore and rejuvenate the dysfunctional vasculature and the damaged organs. Various studies have underlined the important role of bone marrow-derived endothelial progenitor cells (EPCs) in vasculogenesis and angiogenesis of ischemic tissue, but only a few studies have concentrated on the role of EPCs in the prevention and therapy of atherosclerosis. Extended endothelial cell damage by cardiovascular risk factors can result in endothelial cell apoptosis with loss of the integrity of the endothelium. The consequences are an increased vascular permeability of the endothelium followed by facilitated migration of monocytes and vascular smooth muscle cell proliferation, resulting in the premature manifestation of an atherosclerotic lesion. A growing body of evidence suggests that circulating EPCs play an important role in endothelial cell regeneration. Systemic transfusion or intrinsic mobilization of EPCs enhances the restoration of the endothelium after focal endothelial denudation, resulting in a diminished neointima formation. In mice with atherosclerotic lesions, bone-marrow-derived stem cells are able to reduce atherosclerotic plaque size. However, various studies have demonstrated that in humans, cardiovascular risk factors impair number and function of EPCs, potentially restricting the therapeutic potential of progenitor cells. The current review focuses on the role of cardiovascular risk factors on endothelial cell apoptosis and EPCs with its pathophysiological consequences for atherogenesis and a regenerative therapy approach and will highlight the role of EPCs as a marker for cardiovascular mortality and morbidity.     

冠心病患者循环内皮祖细胞与相关危险因素及冠状动脉病变的关系

目的探讨循环内皮祖细胞(EPCs)与冠心病危险因素及冠状动脉病变程度的关系及临床意义。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(>50%的狭窄);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。采集研究对象外周血进行EPCs的分离培养,14天后在倒置相差显微镜下计数细胞克隆形成单位以评估循环EPCs水平,并将EPCs数量与年龄、性别、血脂水平、高血压、糖尿病、吸烟、冠心病家族史及冠状动脉病变程度进行统计学分析。结果冠心病危险因素分数与循环EPCs水平呈明显负相关(r=-0.436,P=0.014),吸烟患者循环EPCs水平明显低于不吸烟者(P<0.05),低密度脂蛋白胆固醇(LDLC)、尿酸与循环EPCs水平呈明显负相关(P<0.05);而性别、高血压、冠心病家族史对循环EPCs水平有一定影响,但差异无统计学意义,年龄、高密度脂蛋白胆固醇(HDLC)及载脂蛋白A(apoA)与循环EPCs水平也有相关性,但不具有统计学意义。冠心病组患者循环EPCs水平明显低于非冠心病组[(12.8±6.3)对(37.0±5.5)个,P<0.001],冠状动脉病变程度(单支、双支、三支)与EPCs水平降低明显相关(P<0.01)。结论循环EPCs水平与冠心病危险因素分数及冠状动脉病变程度呈负相关。提示冠状动脉内皮损伤而又缺乏足够的循环内皮祖细胞时可能影响冠心病的病情程度及临床表现。     

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。     

Effects of haemodialysis on circulating endothelial progenitor cell count

During haemodialysis (HD) the endothelium is the first organ to sense and to be impaired by mechanical and immunological stimuli. We hypothesized that a single HD session induces mobilization of endothelial progenitor cells (EPCs) and that cardiovascular risk factors may influence this process. We quantified EPCs at different maturational stages (CD34+, CD133+/VEGFR2+) in blood samples from 30 patients, during HD and on the interdialytic day, and in 10 healthy volunteers. Samples were drawn at the start of HD, 1, 2 and 3 h after, at the end of HD and at 24 h on the interdialytic day. Patients were divided into two groups based on a recent risk scoring system (SCORE project): low-risk (LR) and high-risk groups (HR). HD patients showed a significantly reduced basal number of EPCs with respect to healthy volunteers. In contrast, we observed increasing EPCs during HD whereas they diminished on the interdialytic day. The EPC number was directly correlated with HD time progression. The EPC number during HD was increased in the HR group with respect to the LR group. We had a direct correlation between risk score and number of EPCs. Cardiovascular risk factors influenced the mobilization of stem cells from the bone marrow. This feature could be the direct consequence of an augmented request of stem cells to respond to the most important endothelial impairment but could also show a defective capacity of EPCs to home in and repair the sites of vascular injury.     

Endothelial progenitor cells: a promising therapeutic alternative for cardiovascular disease

The integrity and functional activity of the endothelial monolayer play a critical role in preventing atherosclerotic disease progression. Endothelial cell (EC) damage by atherosclerosis risk factors can result in EC apoptosis with loss of the integrity of the endothelium. Thus, approaches to repair the injured vessels with the goal of regenerating ECs have been tested in preclinical experimental models and in clinical studies. Indeed, endothelial progenitor cells (EPCs) originating from the bone marrow have been shown to incorporate into sites of neovascularization and home to sites of endothelial denudation. These cells may provide an endogenous repair mechanism to counteract ongoing risk factor-induced endothelial injury and to replace dysfunctional endothelium. Risk factors for coronary artery disease, such as age, smoking, hypertension, hyperlipidemia, and diabetes, however, reduce the number and functional activity of circulating EPCs, potentially restricting the therapeutic prospective of progenitor cells and limiting the regenerative capacity. Furthermore, the impairment of EPCs by risk factors may contribute to atherogenesis and atherosclerotic disease progression. The article reviews the role of EPCs in atherogenesis and in predicting cardiovascular outcomes, and highlights the potential challenges in developing therapeutic strategies aiming to interfere with the balance of injury and repair mechanisms.     

高血压对内皮祖细胞再内皮化能力的影响

目的:探讨高血压对内皮祖细胞粘附、迁移功能及再内皮化能力的影响.方法:选择初发的原发性高血压患者和性别、年龄匹配的健康志愿者各10例,分离其外周血的单个核细胞诱导分化成内皮祖细胞,并通过免疫荧光标记等方法进行形态学观察和鉴定.培养7天后分别观察2组内皮祖细胞的粘附和迁移能力.建立裸鼠颈动脉内皮损伤模型,分别移植健康志愿...     

Circulating endothelial progenitor cells, C-reactive protein and severity of coronary stenosis in Chinese patients with coronary artery disease.

We sought to investigate whether numbers and activity of circulating endothelial progenitor cells (EPCs) correlate with severity of coronary stenosis as well as cardiovascular risk factors in patients with stable coronary artery disease (CAD). Number of circulating EPCs was analyzed in 104 consecutive patients with proven or clinically suspected CAD. Adhesive and migratory activity was also determined. The number of EPCs was lower in patients with a single diseased coronary artery (Group II, n=35, p<0.05 vs. Group I) or multiple diseased arteries (Group III, n=25, p<0.01 vs. Group I, p<0.05 vs. Group II) compared to those with normal coronary arteries (Group I, n=44). The number of EPCs was also related with angiographic Gensini score (r=-0.355, p=0.006). In addition, concentrations of C-reactive protein (CRP) were elevated in patients with CAD, and positively correlated with Gensini score (r=0.476, p=0.001). As for the risk factors, the number of EPCs was also inversely correlated with age (p=0.001), high sensitivity-CRP (p=0.012), hypertension (p=0.042) and family history of CAD (p=0.043). Most importantly, the migratory capacity of EPCs was compromised in patients with CAD, and inversely correlated with the angiographic Gensini score (r=-0.315, p=0.021). EPCs isolated from patients with CAD also showed an impaired adhesive activity (p<0.05). In conclusion, in patients with stable CAD, reduction in the number and impairment in the function of circulating EPCs were correlated with the severity of coronary stenosis. CRP may play an important role in reducing the number of EPCs and accelerating atherosclerosis. Given the important role of EPCs in neovascularization of ischemic tissue, a decrease in the number and activity of EPCs may contribute to the impaired vascularization in patients with CAD.