内皮祖细胞对血管新生的影响及他汀的干预作用

他汀类药物作为传统降血脂药物,其降脂外作用逐渐受到重视,尤其在保护血管内皮功能促进血管新生方面。血管内皮祖细胞作为血管内皮前体细胞,参与出生后血管新生过程,促进血管内皮修复。本文就他汀类药物对血管内皮祖细胞及血管新生影响的研究进展做一综述     

他汀类药物对血管内皮祖细胞的影响机制

血管内皮祖细胞(endothelial progenitor cells,EPCs)是血管内皮的前体细胞,对出生后的血管新生起着非常重要的作用,在缺血性心脏病方面具有良好的应用前景。新近的一些研究证实他汀类药物能增加EPCs的数量,改善EPCs的功能。然而,其作用机制尚未完全阐明。我们就他汀类药物对EP     

他汀类药物对血管新生作用及机制的研究

小剂量他汀类药物能促进骨髓来源内皮祖细胞的动员和分化,提高内皮祖细胞的数量和分化、迁移能力,促进缺血组织血管新生。小剂量他汀类药物可能通过磷脂酰肌醇-3激酶(PI-3K)／苏氨酸激酶(Akt)旁路增加内皮型一氧化氮合酶的表达,从而动员内皮祖细胞。而大剂量他汀类药物可抑制血管新生。     

他汀类药物对血管新生作用及机制的研究

小剂量他汀类药物能促进骨髓来源内皮祖细胞的动员和分化,提高内皮祖细胞的数量和分化、迁移能力,促进缺血组织血管新生.小剂量他汀类药物可能通过磷脂酰肌醇-3激酶(PI-3K)/苏氨酸激酶(Akt)旁路增加内皮型一氧化氮合酶的表达,从而动员内皮祖细胞.而大剂量他汀类药物可抑制血管新生.     

不同剂量阿托伐他汀对稳定型心绞痛患者循环血中内皮祖细胞的影响

目的观察不同剂量的阿托伐他汀对稳定型心绞痛患者循环血中内皮祖细胞数量的影响。方法选取稳定型心绞痛患者84例,分别给予不同剂量的阿托伐他汀10 mg/d、20 mg/d、40 mg/d或80 mg/d治疗共4周。用免疫荧光法检测各组患者用药前后循环血中内皮祖细胞的数量。结果不同剂量的阿托伐他汀应用后内皮祖细胞的数量均较用药前显著性增加(P0.05),并且内皮祖细胞的数量在40 mg/d组最高,与10 mg/d及20 mg/d组相比有显著性差异(P0.05),80 mg/d组较40 mg/d组略有下降,但无统计学差异(P0.05)。结论阿托伐他汀具有剂量依赖性地促进冠心病患者循环血中内皮祖细胞数量增加的作用。     

循环内皮祖细胞在原发性高血压与动脉粥样硬化中的作用

内皮祖细胞(endothelial progenitor cells,EPCs)是来源于骨髓而存在于外周血的单核干细胞,具有分化为成熟内皮细胞功能,参与了内皮损伤修复、血管新生和血管形成等过程,有学者提议用循环内皮祖细胞数量代替C反应蛋白作为新一代预测冠心病的工具.本文主要讨论内皮祖细胞的特性及其在原发性高血压与动脉粥样硬化中的作用.     

脑卒中的一级预防:控制血压、血脂和心力衰竭(续前)

目前,他汀类药物预防脑卒中的机制尚未完全清楚。他汀类药物独立降脂以外的多效性可能与减少炎症、抗动脉粥样硬化、降低血压、稳定斑块、抗血栓、改善纤溶活性、降低血小板活性有关。他汀类药物还具有免疫调节作用,增加循环内皮祖细胞的数量,并改善     

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.     

冠心病患者内皮祖细胞数量及功能变化的研究进展

冠心病(CHD)是现代社会严重威胁人类健康的主要疾病之一,且病死率高。动脉粥样硬化（AS）是其病理基础。而内皮细胞的损伤与CHD的发生发展关系密切。血管内皮祖细胞(endothelial progenitor cells,EPCs)作为内皮细胞的前体细胞,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,在冠心病发生及发展过程中起着非常重要的作用。已经证明EPCs数量下降及功能减退与CHD发病有密切关系,现将冠心病患者外周血内皮祖细胞数量及功能的变化情况做一详细阐述。     

基因转染内皮祖细胞治疗心血管病

人体外周血中内皮祖细胞的数量有限,基因转染能增强内皮祖细胞的增殖性以及功能。本文综述移植内皮祖细胞在治疗肢体缺血、防治冠心病、改善糖尿病患者的血管形成能力的作用。     

内皮祖细胞参与兔动脉瘤模型血管的修复

目的探讨内皮祖细胞（EPCs）是否参与兔动脉瘤血管损伤的修复过程。方法取清洁级兔10只,利用弹性酶诱导动脉瘤模型。按照EPCs回输方式不同,随机分为颈动脉原位回输组和耳缘静脉回输组,每组5只。自体培养EPCs后,用Hoechst33342和羟基荧光素二醋酸盐琥珀酰亚胺脂（CFSE）对细胞进行双标记。采用荧光染色、HE染色、免疫组化等方法分析EPCs参与新生内膜修复的过程。结果①培养的EPCs经Hoechst33342和CFSE双标记后,颈动脉原位回输组自体回输EPCs（1．45±0．09）×10^6个,耳缘静脉回输组自体回输EPCs（1．47±0．17）×10^6个。②颈动脉原位回输组的动脉瘤内血栓中及新生内膜内均可见双标记的细胞直接黏附（5／5）,内膜表面未见内皮细胞生长。③静脉回输组的部分动脉瘤壁新生内膜内（非内膜表面）可见到双标记细胞（3／5）,未见有内皮细胞生长。④两组动脉瘤组织的HE染色均未见内膜上皮样细胞分布,免疫组织化学均显示内膜Von Willebrand因子（vwF）染色阴性。结论EPCs参与了动脉瘤损伤血管的早期内膜修复,但未以转化成内皮细胞形式参与修复。     

How to accelerate the endothelialization of stents

Coronary artery stenting is currently the most frequently performed percutaneous coronary intervention for the treatment of coronary artery disease. The endothelium is a single layer of endothelial cells lining the vascular wall and plays an integral part in maintaining vascular homeostasis. Stenting however causes significant injury to the vascular wall and endothelium, resulting in inflammation, repair and the development of neointimal hyperplasia. The ability of the endothelium to repair itself depends on both the migration of surrounding mature endothelial cells, and the attraction and adhesion of circulating endothelial progenitor cells (EPCs) to the injured region, which then differentiate into endothelial-like cells. Current therapies with drug-eluting stents interrupt the natural response to damage. Accelerating the reendothelialization of the damaged arterial segment following stent implantation is an attractive form of therapy as it is seen as hastening the natural process of repair. It potentially has the benefit of reducing the amount of neointimal hyperplasia and stent thrombosis. Studies have been performed to identify agents that augment the mobilisation and recruitment of EPCs to the injured area (statins, exercise, estrogen and cytokines). Other studies have looked at seeding stents with endothelial cells or EPCs. The most current approach is to coat anti-CD34 antibodies on a stent surface to attract circulating EPCs to the stent which then differentiate into endothelial-like cells. This approach is currently being tested in safety and feasibility clinical studies.     

Endothelial progenitor cells: mobilization,differentiation, and homing

Postnatal bone marrow contains a subtype of progenitor cells that have the capacity to migrate to the peripheral circulation and to differentiate into mature endothelial cells. Therefore, these cells have been termed endothelial progenitor cells (EPCs). The isolation of EPCs by adherence culture or magnetic microbeads has been described. In general, EPCs are characterized by the expression of 3 markers, CD133, CD34, and the vascular endothelial growth factor receptor-2. During differentiation, EPCs obviously lose CD133 and start to express CD31, vascular endothelial cadherin, and von Willebrand factor. EPCs seem to participate in endothelial repair and neovascularization of ischemic organs. Clinical studies using EPCs for neovascularization have just been started; however, the mechanisms stimulating or inhibiting the differentiation of EPC in vivo and the signals causing their migration and homing to sites of injured endothelium or extravascular tissue are largely unknown at present. Thus, future studies will help to explore areas of potential basic research and clinical application of EPCs.     

Vascular repair by endothelial progenitor cells

Accumulating evidence indicates the impact of endothelial progenitor cells (EPCs) in vascular repair. In patients, the number of EPCs is negatively correlated with the severity of atherosclerosis. In various animal models, transplantation of bone marrow-derived progenitor cells could sufficiently rescue organ function and enhance vascular repair and tissue regeneration. Increase in the number of circulating progenitors, induced by cell transfusion or enhanced mobilization, can also enhance restoration and integrity of the endothelial lining, suppress neointimal formation, and increase blood flow to ischaemic sites. However, the beneficial outcome of EPC infusion very much depends on the growth and differentiation factors within the tissue, cell-to-cell interactions, and the degree of injury. As highlighted by several studies, EPCs derive from different sources including bone marrow and non-bone marrow organs such as the spleen, the functional repair properties of which may vary with the maturation state of the cell. Thus, understanding the molecular mechanisms involved in EPC-repairing processes is essential. In the present review we focus on the role of EPCs in vascular diseases, and we provide an update on the mechanisms of EPC mobilization, homing, and differentiation.     

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.     

他汀药物在早期经皮冠状动脉介入治疗中的作用

他汀药物除降脂作用外,还具有抗凝和抗血小板聚集、改善内皮功能、调节一氧化氮活性、稳定斑块以及抗炎等作用,即他汀药物的"多效性"。经皮冠状动脉介入治疗是冠状动脉粥样硬化性心脏病治疗中一个重要的治疗方法,但冠状动脉介入治疗过程中会导致血管壁损伤,激发血小板活性,导致微血栓形成,引起血管壁和微脉管系统末梢炎性反应等一系列不良反应。他汀药物的"多效性"可能会减少介入治疗导致的主要不良心血管事件的发生,达到改善冠状动脉粥样硬化性心脏病预后的目的。     

The cardioprotective effects of statins

In addition to their lipid-modulating properties, statins have a large number of beneficial cardiovascular effects that have emerged over time and that were not anticipated during drug development. The lipid and nonlipid effects act in a concerted way to reduce the ischemic burden of the myocardium and to protect it against injury. By acting on the vessel wall, statins may prevent lesion initiation and repair injuries, enhance myocardial perfusion, slow lesion progression, and prevent coronary occlusion. They may also directly reduce myocardial damage, favor myocardial repair, and protect against immune injury. This review focuses on properties of statins that contribute to their cardioprotective effect. The first section includes information on modulation of vascular tone, endothelial permeability and function, inhibition of complement injury, curbing of foam cell formation, antioxidant and anti-inflammatory properties, and profibrinolytic and anticoagulant activities. The second section relates to reduction of myocardial necrosis, myocardial hypertrophy, blood pressure, and heart failure, as well as mobilization of endothelial progenitor cells for repair, angiogenic effects, and immunomodulation. In many instances, results of in vitro and animal studies have raised expectations and prompted studies in humans. Several clinical trials have confirmed these expectations and have strengthened the value of statins as valuable antiatherosclerotic and cardioprotective agents.     

Therapeutic potential of endothelial progenitor cells in cardiovascular diseases

Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising.     

Biologic properties of endothelial progenitor cells and their potential for cell therapy

Recent studies indicate that portions of ischemic and tumor neovasculature are derived by neovasculogenesis, whereby bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) home to sites of regenerative or malignant growth and contribute to blood vessel formation. Recent data from animal models suggest that a variety of cell types, including unfractionated BM mononuclear cells and those obtained by ex vivo expansion of human peripheral blood or enriched progenitors, can function as EPCs to promote tissue vasculogenesis, regeneration, and repair when introduced in vivo. The promising preclinical results have led to several human clinical trials using BM as a potential source of EPCs in cardiac repair as well as ongoing basic research on using EPCs in tissue engineering or as cell therapy to target tumor growth.