血管新生与缺血性心脏病

本文阐述了一种治疗缺血性心脏病新方法——血管新生疗法的理论依据、动物实验及临床研究的现状,尤其强调血管生长因子基因疗法的优越性及良好的应用前景。     

血管内皮祖细胞和血管新生的研究进展

存在于外周血的血管内皮祖细胞参与血管新生的事实已被多方实验所证实，这为治疗心肌缺血开辟了新途径。本文主要就这方面的研究进行了综述。     

细胞生长因子与血管新生在缺血性心脏病中的研究进展

众多生长因子参与新生血管生长过程的调节。通过新血管生成，建立冠脉侧枝循环，对缺血性心脏病的治疗具有重要积极的意义。     

外膜滋养血管新生的病理机制

<正>外膜是集成血管壁功能的主要监管机构,可以充当生物"中央处理器",外膜分布有多种细胞能够发挥强效免疫调节作用,包括成纤维细胞、巨噬细胞、树突状细胞、祖细胞、滋养血管以及肾上腺素能神经。成纤维细胞的激活能够促进巨噬细胞、树突状细胞、祖细胞作用的发挥,创建一个持久的炎症反应的微环境,引起滋养血管的新生〔1〕。由于研究血管滋养管的适合方法有限,观察动脉壁上微血管新生的病理生理环境也知之甚少。本文就今年来关于外膜滋养血管(VV)新生的生理、病理     

细胞和血管生长因子致血管新生在缺血性心脏病中的应用

各种细胞或血管生长因子能够致血管新生进而治疗缺血性心脏病,在过去的二三十年里,该领域取得了相当程度的进展。本文就近期的基础和临床研究进行了总结。     

血管抑素和内皮抑素抑制肿瘤血管新生的动物实验研究

目的　建立小鼠背部开窗模型 ,在直视下观察肿瘤生长情况及血管抑素 (AS)和内皮抑素 (ES)对肿瘤的影响。方法　免疫组化测定血管内皮细胞生长因子 (VEGF)、细胞表面磷酸化糖蛋白 (CD34 )的表达 ,了解肿瘤血管生长的情况。结果　本实验肿瘤细胞移植 1 3d后 ,对照组所有小鼠移植肿瘤均生长状态良好 ,肿瘤的生长已使小鼠的行动发生困难 ;而给药组肿瘤小 ,行动不受限制 ,也未见到药物副作用的表现。给药组肿瘤的生长被明显抑制 ,其肿瘤体积小 ,重量明显减轻 .。高剂量给药组与对照组间有显著性差异 (P<0 .0 1 ) ;而且抑制肿瘤生长的作用亦明显高于低剂量对照组 (P<0 .0 1 ) ;高剂量给药组肿瘤中心发生坏死也比较明显。结论　成功建立开窗可视模型 AS、ES抑制肿瘤血管新生起重要作用。     

Angiopoietin/Tie2系统在血管新生与成熟过程中的表达及意义

血管的新生和成熟需要经过血管内皮细胞与血管周围细胞间相互作用等一系列复杂的生物学过程,这一过程受到多种细胞因子的调控。促血管生成素(angiopoietin,Ang)是近年发现的一个与血管新生与成熟密切相关的家族,包括4个成员,即Ang1、Ang2、Ang3和Ang4,其共同的特异性受体为Tie2。Ang及受体Tie2在生理性血管形成过程中对新生血管的形成、重构及成熟发挥重要的调控作用。另有研究显示,Ang/Tie2系统也参与了缺血后再灌、肿瘤及视网膜病变等多种病理性血管的形成过程。研究Ang/Tie2系统的生物学效应以及其在血管新生与成熟过程中的表达及意义,有助于深入了解相关疾病的发病机制并为疾病的治疗提供新线索。     

血管特异性生长因子与缺血性脑血管病的治疗

单一应用血管内皮生长因子(VEGF)治疗缺血性脑血管病有一定疗效,但也存在一些问题。VEGFF和血管生成素可在局灶性脑缺血中共同发挥作用。因此,在缺血性脑血管病中的治疗中,综合应用这些血管特异性生长因子可能更有前景。     

血管内皮祖细胞与老年缺血性心血管病的血管新生

<正> 1997年国内外报道血管内皮祖细胞(endothelial progenitorcelhs,EPCs)分离培养成功,从而使:EPCs成为当前干细胞研究热潮中的一个分支。EPCs是一群具有游走性特征、能进一步增殖分化的幼稚内皮细胞,由干细胞经成血管细胞分化发育而来,由于缺乏成熟内皮细胞的特征性表型,因此,有人提出对于EPCs的鉴别分离主要靠其特异性的分子标志(CD34+、flk-1、AC133+);此外也可通过EPCs培养分化形     

血管抑素治疗眼部新生血管疾病研究进展

眼部新生血管疾病是各种致病因素所引起的眼部并发症，是目前常见的致盲原因之一。近年研究发现，血管生成抑制因子一血管抑素(angiostatin As)是迄今发现的最有效的血管生成抑制剂之一。现对其临床应用进展综述如下。     

Pathophysiology of ischemic heart disease

Recent clinical and experimental studies have helped to clarify the pathophysiology of acute and chronic coronary insufficiency, particularly in the area relating myocardial ischemia to abnormal function of the damaged left ventricle. When proximal vessel stenosis due to coronary atherosclerotic disease becomes the major locus of resistance to coronary blood flow, there is a decline in perfusion pressure distal to the stenosis. This results in ischemia when the normal mechanism for autoregulating coronary flow (i.c., coronary arteriolar vasodilatation) is no longer adequate to maintain flow.     

缺血性心脏病促血管生成治疗方法的研究进展

［摘要］　缺血性心脏病（IHD）,也称为冠心病,是由冠状动脉狭窄或阻塞引起的一组疾病。治疗IHD诱导血管生成和血管重建至关重要。近年来研究表明,外泌体可以通过促进血管生成,从而减轻心肌缺血再灌注损伤,抑制纤维化和促进心脏再生等作用,对IHD具有保护作用。促血管生成的研究可能为IHD的治疗提供新的选择。该文对IHD促血管生成治疗方法的研究进展作一综述。     

Pathophysiology of atherosclerotic heart disease

Coronary atherosclerosis is the major health problem of the twentieth century. Although there has been a recent decrease in mortality from this condition in many Western countries, the incidence has remained the same, and coronary atherosclerosis continues to be the leading cause of death. Our understanding of the disease process has been steadily increasing; however, much still needs to be clarified. The clinical presentations of coronary artery disease are diverse and not clearly linked to the severity or extent of the disease. Patients with similar coronary lesions present variously with stable and unstable angina or myocardial infarction, and all too many have sudden death as the initial clinical presentation. Recently, much attention has focused on the initial events leading to the development of atherosclerotic plaques. Current concepts unite formerly opposed views on the roles of intimal injury, platelets, lipids, and monoclonal smooth muscle cell proliferation in initiating atherogenesis. Progress has been made in understanding the early structural and functional alterations caused by myocardial ischemia. This understanding is leading to the development of interventions such as intracoronary thrombolysis to prevent or limit permanent myocardial injury. Measures to prevent serious complications of ischemic heart disease such as infarct rupture, aneurysm formation, and ischemic cardiomyopathy are still needed.     

Therapeutic angiogenesis for ischemic cardiovascular disease

In animal models of ischemia, a large body of evidence indicates that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. While many cytokines have angiogenic activity, the best studied both in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown large increases in exercise time and marked reductions in symptoms of angina, as well as objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein, and have not yet shown significant improvement in either exercise time or angina when compared to placebo. Larger scale placebo-controlled studies of gene transfer are in progress. Future clinical studies will be required to determine the optimal dose, formulation, route of administration and combinations of growth factors, as well as the requirement for endothelial progenitor cell or stem cell supplementation, to provide effective and safe therapeutic myocardial angiogenesis.     

雌激素与缺血性心脏病

以往的临床观察证实 ,生育年龄的女性缺血性心脏病的发病率和死亡率明显低于同龄男性。绝经后的妇女服用雌激素与不服用雌激素相比 ,前者心脏病事件少于后者。尽管临床的观察结果还有争议 ,越来越多的临床前期研究表明 ,雌激素对缺血性心脏病具有保护作用。研究结果显示 ,雌激素和其受体调节器是通过减少炎性反应在缺血/再灌注引起心肌损伤时起保护作用的。本文作者就近年的一些研究结果作一综述 ,并就雌激素替代治疗处理心肌缺血及再灌注损伤进行探讨。     

抑郁与缺血性心脏病

随着传统的生物医学模式向生物-心理-社会的现代医学模式的转变，人们认识到大量的心理社会因素和疾病密切相关。对抑郁与缺血性心脏病之间关系的研究是近年来国外研究的热点，本文试从流行病学，病理生理学、分子生物学和治疗四个方面对相关的的研究进行综述。     

Angioscopy and ischemic heart disease

Angioscopy allows direct visualization of the coronary artery lumen and provides detailed information regarding the surface characteristics of the vessel wall and specific lesions causing acute coronary syndromes. Disruption of a plaque, ulceration, tears, fissures, lipid-rich or fibrous lesions, and luminal or mural thrombus can be readily detected in vivo. Characterization of culprit lesions in various coronary syndromes reveals the different mechanisms of ischemia. The predominant lesion in acute myocardial infarction is an ulcerated, yellow plaque with thrombus. In unstable angina, different substrates can be seen, from the lipid-rich lesion with thrombus to the fibrous smooth plaque, reflecting a varied physiopathology. Because of its ability to detect superficial lipid pools, angioscopy may be valuable for the detection of vulnerable plaques.     

Prostaglandins and ischemic heart disease

There is an abundance of information suggesting that prostaglandins are involved in the development and clinical expression of atherosclerosis. Many studies demonstrate a relationship between prostaglandins and the risk factors for peripheral and coronary artery disease. Thus, part of the mechanism by which hyperlipidemia, diabetes mellitus, smoking, hypertension, sex hormones, age, heredity, emotional stress and diet contribute to the development and progression of atherosclerosis may be through an imbalance between thromboxane A₂ and prostaglandin I₂. Recent studies show a temporal relationship between acute ischemic events (specifically, unstable angina) and a transcardiac increase in thromboxane B₂, while others demonstrate a salutary effect of disaggregatory and vasodilatory prostaglandins in such patients. If prostaglandins and thromboxane prove important in ischemic vascular disease, attention will be directed at the correction of their pathologic imbalance. This may be accomplished by dietary manipulation as well as by the development of prostaglandin receptor antagonists or inhibitors of specific prostaglandin pathways.