Basic Concepts of (Myocardial) Angiogenesis: Role of Vascular Endothelial Growth Factor and Angiopoietin.
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.
Carmeliet
P
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, B-3000, Belgium.