血管内皮生长因子介导的血管新生疗法在心血管疾病中的研究进展

冠心病、心肌梗死等缺血性心血管疾病严重威胁人类健康,而促血管新生疗法作为一种新颖的治疗策略,可能为难以接受传统血管重建治疗的患者提供全新的治疗模式。血管内皮生长因子(vascular endothelial growth factor,VEGF)是目前已知最强的促血管生长因子,在促血管新生治疗方面具有重要作用。本文重点介绍VEGF与缺血性心血管疾病(包括心肌梗死、冠状动脉粥样硬化和斑块内血管新生)的关系以及VEGF基因疗法在缺血性心血管疾病治疗中的应用。     

血管内皮生长因子与缺血性心血管疾病

血管内皮生长因子与缺血性心血管疾病郑卫李倩虹陈光慧汤健马大龙１９８９年Ｇｏｓｐｏｄａｒｏｗｉｃｚ等［１］首先从牛垂体滤泡星状细胞培养液中纯化出一种蛋白质，由于其具有促进内皮细胞有丝分裂和血管生长的作用，故命名为血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄ...     

叶酸干预血管内皮功能障碍的研究进展

血管内皮功能障碍与诸多心血管疾病的发生、发展有密切联系,被认为是心血管疾病危险的终点替代指标。内皮功能障碍的研究和血管内皮的保护成为目前研究的热点。叶酸,一种经济无毒的药物,能明确改善血管内皮功能。其可能机制有降低血浆同型半胱氨酸、抗氧化作用、对内皮型一氧化氮合酶作用等,其对心血管疾病的预防具有重要意义。     

血管内皮功能失调与心血管疾病

随着基础研究的进展,人们对血管内皮功能的认识日渐深入,血管内皮既是众多心血管疾病危险因子作用的靶器官,其功能失调又构成许多心血管疾病的病理基础,因此,如何保护血管内皮功能已成为治疗心血管疾病的重要目标之一。     

血管内皮祖细胞在心血管疾病中的研究进展

血管内皮祖细胞是血管内皮细胞的前体细胞,又称为血管母细胞。不仅参与胚胎血管生成,也参与出生后的血管发生过程。应用血管内皮祖细胞进行细胞移植是目前治疗缺血性血管病变的研究热点,已有报道开始应用于临床。现就血管内皮祖细胞在心血管疾病中的研究现状做一综述,同时对干细胞移植存在的安全性、靶向性、效应性方面的问题以及如何开发一种新型的干细胞移植技术做一评价和展望。     

内皮祖细胞与缺血性心脏病

缺血性心脏病是一类严重威胁人类健康的疾患,其发生、发展和预后与血管内皮密切相关。研究发现内皮祖细胞也参与出生后的内皮修复和血管新生过程,提示其在缺血性心脏病中的重要治疗作用和临床运用前景。     

内皮素和一氧化氮在心血管病中的作用

心血管疾病与血管内皮的关系已被医务界所认识 ,血管内皮所分泌的内皮素— 1及一氧化氮在心血管疾病的发病中起重要作用。所以 ,保护血管内皮功能可以预防心血管疾病     

运动与内皮祖细胞

内皮祖细胞可以分化成为血管内皮细胞,具有保护血管内皮,减少心血管疾病的发病率和死亡率的作用。无论是在健康人群中,还是在心血管疾病患者中,运动可以使外周血中内皮祖细胞的数量增多、功能改善,进而保护血管内皮。运动引起内皮祖细胞增加的机制尚不明确,血管内皮细胞生长因子和一氧化氮,可能在其中发挥作用。     

内皮祖细胞在心血管疾病的研究进展

内皮细胞的脱失和功能障碍是心血管疾病中的突出特征。血管内皮祖细胞起源于骨髓,对于缺血组织的血管新生和损伤血管的复内皮化起着很重要的作用。现主要综述内皮祖细胞在心血管疾病中的应用及存在问题。     

骨髓间充质干细胞促进受损血管内皮修复的相关问题

血管内皮损伤是心血管疾病发病及介入治疗后再狭窄发生的病理基础,防治内皮损伤及促进受损内皮修复是目前心血管疾病研究的重点。骨髓间充质干细胞由于其多向分化及自我更新特性受到研究者的关注。本文仅对骨髓间充质干细胞促进受损血管内皮修复方面作一综述。     

Stem cells and the regeneration of the aging cardiovascular system

It is well established that cardiovascular repair mechanisms become progressively impaired with age and that advanced age is itself a significant risk factor for cardiovascular disease. Although therapeutic developments have improved the prognosis for those with cardiovascular disease, mortality rates have nevertheless remained virtually unchanged in the last twenty years. Clearly, there is a need for alternative strategies for the treatment of cardiovascular disease. In recent years, the idea that the heart is capable of regeneration has raised the possibility that cell-based therapies may provide such an alternative to conventional treatments. Cells that have the potential to generate cardiomyocytes and vascular cells have been identified in both the adult heart and peripheral tissues, and in vivo experiments suggest that these cardiovascular stem cells and cardiovascular progenitor cells, including endothelial progenitor cells, are capable of replacing damaged myocardium and vascular tissues. Despite these findings, the endogenous actions of cardiovascular stem cells and cardiovascular progenitor cells appear to be insufficient to protect against cardiovascular disease in older individuals. Because recent evidence suggests that cardiovascular stem cells and cardiovascular progenitor cells are subject to age-associated changes that impair their function, these changes may contribute to the dysregulation of endogenous cardiovascular repair mechanisms in the aging heart and vasculature. Here we present the evidence for the impact of aging on cardiovascular stem cell/cardiovascular progenitor cell function and its potential importance in the increased severity of cardiovascular pathophysiology observed in the geriatric population.     

内皮前体细胞移植:冠心病治疗的新策略

干细胞研究的进展和基因治疗技术在心血管的应用为缺血性心脏病的治疗提供了新策略。基因修饰后内皮前体细胞移植既补充了功能不良且数量不足的内皮前体细胞又诱导并促进了局部新血管的生成 ,展示了美好的临床应用前景。本文回顾了近几年来缺血性心脏病治疗的新概念 ,重点介绍了国外内皮前体细胞及其基因修饰应用的新进展 ,并对存在的问题和应用前景分别进行了讨论和展望     

Endothelium-targeted gene and cell-based therapies for cardiovascular disease

Most common cardiovascular diseases are accompanied by endothelial dysfunction. Because of its predominant role in the pathogenesis of cardiovascular disease, the vascular endothelium is an attractive therapeutic target. The identification of promoter sequences capable of rendering endothelial-specific transgene expression together with the recent development of vectors with enhanced tropism for endothelium may offer opportunities for the design of new strategies for modulation of endothelial function. Such strategies may be useful in the treatment of chronic diseases such as hypertension, atherosclerosis, and ischemic artery disease, as well as in acute myocardial infarction and during open heart surgery for prevention of ischemia and reperfusion (I/R)-induced injury. The recent identification of putative endothelial progenitor cells in peripheral blood may allow the design of autologous cell-based strategies for neovascularization of ischemic tissues and for the repair of injured blood vessels and bioengineering of vascular prosthesis. "Proof-of-concept" for some of these strategies has been established in animal models of cardiovascular disease. However the successful translation of these novel strategies into clinical application will require further developments in vector and delivery technologies. Further characterization of the processes involved in mobilization, migration, homing, and incorporation of endothelial progenitor cells into the target tissues is necessary, and the optimal conditions for therapeutic application of these cells need to be defined and standardized.     

Cell therapy for cardiovascular disease: what cells, what diseases and for whom?

Experimental and human data suggesting progenitor cells possess the capacity to regenerate tissue and augment repair in injured organs has generated widespread interest in the basic research and clinical communities. Nowhere have these findings been more tantalizing than in human cardiovascular disease, in which vasculogenesis and myocardial regeneration logically and understandably remain as attractive therapeutic targets. Burgeoning experimental evidence attests to the proangiogenic, vasculogenic and tissue reparative capabilities of a broad range of progenitor cells derived from the bone marrow, circulation and a number of other tissues in vivo. Studies demonstrating the most apparent therapeutic success are those implicated in revascularization and repair of acute or chronically ischemic tissues in the heart and the peripheral vascular system. Numerous small clinical trials have yielded promising preliminary results without clear evidence of a superiority for a specific cell type or clinical disease entity as the most suitable target for cell therapy. This review will evaluate the scientific rationale for use of a specific cell or cells, the cardiovascular disease states most appropriate for targeted cell therapy, and the patient-specific barriers to therapeutic success, including emerging hurdles such as cardiovascular risk factors and comorbidities in eligible subjects.     

Aging and disease as modifiers of efficacy of cell therapy

Cell therapy is a promising option for treating ischemic diseases and heart failure. Adult stem and progenitor cells from various sources have experimentally been shown to augment the functional recovery after ischemia, and clinical trials have confirmed that autologous cell therapy using bone marrow-derived or circulating blood-derived progenitor cells is safe and provides beneficial effects. However, aging and risk factors for coronary artery disease affect the functional activity of the endogenous stem/progenitor cell pools, thereby at least partially limiting the therapeutic potential of the applied cells. In addition, age and disease affect the tissue environment, in which the cells are infused or injected. The present review article will summarize current evidence for cell impairment during aging and disease but also discuss novel approaches how to reverse the dysfunction of cells or to refresh the target tissue. Pretreatment of cells or the target tissue by small molecules, polymers, growth factors, or a combination thereof may provide useful approaches for enhancement of cell therapy for cardiovascular diseases.     

Regeneration of the vascular compartment

Throughout life, damage to the vascular endothelium is pivotal in the development of cardiovascular disease. Therefore, a detailed understanding of the underlying mechanisms involved in endothelial cell restoration is of fundamental importance for preventive and therapeutic concepts in cardiovascular disease. The goal of regenerative medicine is the use of tissue-specific progenitor cells for a more effective repair process with reduction of fibrocellular remodelling, fibrosis and loss of functional properties. According to the hitherto assumed primary model of endothelial regeneration only adjacent and intact mature endothelial cells replace damaged endothelium. Since Asahara and colleagues first described that a peripheral blood mononuclear cell population was able to differentiate into endothelial cells in vitro and incorporate into ischemic tissue at sites of angiogenesis in vivo, the model of endothelial regeneration has been extended. The majority of clinical trials on human cell therapy for ischemic vascular disease are based on cell surface antigen expression of CD34 or VEGFR2 to identify endothelial progenitor cells. A precise characterization of the angiogenic properties of different subsets of endothelial regenerating cells and their course of action to gain sufficient long-term regeneration of the injured vessel is a necessary precondition before clinical trials of human cell therapy become a routine reality.     

祖细胞和干细胞与缺血性疾病的治疗

缺血性疾病是严重危害人类健康的疾病之一,主要包括缺血性脑血管疾病、缺血性心血管疾病、下肢缺血性疾病等。祖细胞和干细胞都是具有自我复制能力的多潜能细胞,在一定条件下,它们可以分化成多种功能细胞。根据干细胞所处的发育阶段分为胚胎干细胞和成体干细胞,虽然胚胎干细胞具有万能分化型功能,但伦理学方面的争议使其研究困难重重,而成体干细胞相较胚胎干细胞,不仅避免了伦理学方面的争议问题,而且无移植后免疫排斥反应。本文主要讨论成体干细胞和祖细胞在缺血性疾病中的应用。近年来,关于祖细胞和干细胞在缺血性疾病中应用的研究日益增多,受到了广泛的关注,为我们提供了一条治疗缺血性疾病的新思路。     

Stem cell therapy in cardiovascular disorders

Heart insufficiency remains the leading cause of death despite pharmacological and interventional therapy as well as primary and secondary prevention. Laboratory research on cardiac repair implementing stem cells and progenitor cells has raised great expectations as well as controversies. The potential of diverse progenitor cells to repair damaged heart tissue includes replacement (tissue transplant), restoration (activation of resident cardiac progenitor cells, paracrine effects), and regeneration (stem cell engraftment forming new myocytes). Based on promising experimental results clinical trials including several hundreds of patients with ischemic heart disease have been initiated using mostly bone marrow-derived cells. Probably, due to a lack of standardization of cell isolation and delivery methods these trials showed controverse results regarding effectiveness. However, significant therapeutic regeneration of human myocardium could not be proven until now. Several issues are at debate concerning the translation of the experimental data into the clinic discussing the adequate cell type, dosing, timing, and delivery mode of myocardial stem cell therapy. This review focuses on the potential and clinical translation of cell based therapies in cardiovascular disease.     

Advances in cell-based therapy for peripheral vascular disease

Evidence is accumulating to support cell-based therapies as a new approach for chronic diseases. Perhaps the area of greatest impact, in terms of patient numbers, is cardiovascular disorders. This review considers cell transplantation as a potential treatment for peripheral vascular disease, including ischemic stroke and erectile dysfunction. Bone marrow derived cells are required for endogenous repair in adult individuals affected by angiopathies. Clinical trials using progenitor cells generated from monocytic or non-monocytic cells indicate that both are effective, suggesting that angiogenesis is the result of cross talk between different cells and pathways. Currently, there are 14 registered clinical trials (ClinicalTrials.gov) examining different approaches to stem cell therapy to cure peripheral artery disease, of which 6 have completed enrollment. Here, we will review published clinical studies that used cell transplantation for peripheral vascular ischemic disorders.