Basic Concepts of (Myocardial) Angiogenesis: Role of Vascular Endothelial Growth Factor and Angiopoietin.

Carmeliet
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Abstract

Blood vessels are essential for the supply of oxygen and nutrients to the heart. An imbalance between oxygen demand and supply (ischemia), as occurs when coronary arteries become obstructed by atherosclerotic plaques, triggers a response to improve myocardial perfusion by the formation of new capillaries (angiogenesis) and by the enlargement of preexisting collateral vessels (arteriogenesis). Recently, novel insights have been obtained in the molecular mechanisms of angiogenesis and in its control by hypoxia. This has lead to the design of strategies to improve myocardial perfusion. However, rational design of therapeutic angiogenesis mandates a better understanding of the molecular basis of angiogenesis. This review discusses the role of two prime classes of angiogenic molecules, namely of vascular endothelial growth factor (VEGF) and angiopoietin (Ang), and addresses novel insights in the regulation of angiogenesis by hypoxia. In addition, a novel mouse model of ischemic cardiomyopathy with signs of hibernation is presented. Possible implications for therapeutic myocardial angiogenesis are discussed.

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心肌血管生成的基本概念:血管内皮生长因子和血管生成素的作用。
血管是向心脏供应氧气和营养物质所必需的。当冠状动脉被动脉粥样硬化斑块阻塞时,氧气需求和供应之间的不平衡(缺血)会通过形成新的毛细血管(血管生成)和扩大原有的侧支血管(动脉生成)来引发改善心肌灌注的反应。近年来,人们对血管生成的分子机制和缺氧对血管生成的控制有了新的认识。这导致了改善心肌灌注策略的设计。然而,合理设计治疗性血管生成需要更好地理解血管生成的分子基础。本文讨论了血管内皮生长因子(VEGF)和血管生成素(Ang)两类主要血管生成分子的作用,并提出了缺氧对血管生成调节的新见解。此外,还提出了一种具有冬眠体征的缺血性心肌病小鼠模型。讨论了治疗性心肌血管生成的可能意义。
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