Preconditioning and Myocardial Angiogenesis

摘要

Summary. In the Western World ischemic coronary disease is the leading cause of morbidity and mortality. Therapeutic approaches mostly aim to restore flow to a localized segment by angioplasty or bypass surgery. In order to develop better arid more effective therapeutic strategies using the powerful concept of inducing new vessel growth or by employing vascular growth factors, it is essential to further our understanding of the molecular mechanisms and the chain of events underlying the fascinating process of angiogenesis. Among the various triggers of angiogenesis, tissue hypoxia/ischemia has been identified as being a particularly important stimulus for the induction of new vessel growth. Occlusion of a main coronary depletes the blood supply to the myocardium and subsequently reduces cardiac function, which ultimately leads to heart failure. Progressive, chronic coronary artery occlusion has been shown to induce development of collateral arteries to reestablish and maintain blood flow to the myocardium at risk via the growth of new capillary vessels or angiogenesis. Studies from our laboratory as well as from, others have already confirmed the protective role of collaterals against myocardial ischemia and cell death. We have successfully demonstrated in adult rat myocardium (LV) effects of hypoxia/reoxygenation on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors (Flk-1 and Flt-1) as well as other angiogenic factors such as Ang-1, Ang-2 and their receptor Tie-2. Also, we were able to demonstrate increased capillary/arteriolar density, increased capillary to myocyte cross-sectional area (after 1-4 weeks and after 2 months) and decreased collagen volume fraction by hypoxic/ischemic preconditioning in a rat model of chronic myocardial infarction (MI) model.