| lschemic heart disease (IHD) is a major cause of mortality and morbidity in humans. IHD is characterized by inadequate blood flow and tissue oxygenation that is typically the consquence of decreased patency of atherosclerotic vessels, which results in angina, myocardial infarction, arrhythmia and heart failure. Traditionally, patients with IHD requiring a revascularizing procedure have had to undergo either coronary artery bypass surgery (CABG), which usually involves open thoracotomy, or percutaneous transluminal balloon angioplasty (PTCA), or medicine treatment. Despite the last few decades have seen the development of three methods just described, a large number of patients especially patients with severe diffuse coronay heart disease, absent conduits after bypass surgery, small distal vessels, and unacceptably high operative risks, were not candidates for direct revascularization. It has been estimated that over 5% of patients were not eligible for conventional therapies. The discoveries of various angiogenic growth factors brought hopes to IHD patients. It has been shown that myocardial ischemia induced the production of growth factors and formed a few collateral vessels but couldn's meet the oxygen need of ischemic myocardium. Increases in coronary collateral blood flow by growth adaptation of preexisting coronary collaterals or neovascularization may reduce myocardial ischemia, prevent infarction, and preserve contractile function. Thence, intense investigation has been directed towards enhaning the development of coronary collaterals by exogenous administration of growth factors and gene therapy. Primary results showed that therapeutic angiogenesis became promise as a potential modality to treat myocardial ischemia. A number of phase I safety studies have been reported in which angiogenic factors or the genes cncoding these factors have been administered to patients in small numbers. This strategy may represent a new approach to the treatment of ischemic cardiovascular disease. The growth factors that have been investigated for new blood vessel formations included the vascular endothelial growth factors (VEGF), fibroblast growth factors (FGF), and the angiopoietins. Certainly, these growth factors are capable of inducing physiologically significant angiogenesis. It is not yet clear whether one of these agents is better than others because of difference in biological character. Vascular endothelial growth factor B was a newly discovered growth factor that shows close homology to VEGF. VEGF-B is expressed in various tissues, especially strongly in the heart, and binds selectively to one of the VEGF receptors VEGFR- land neuropilin- 1. Some studies have demonstrated that mRNA coding VEGF-B was present in endothelial cells and pericytes. The ability of VEGF-B to stimulate endothelial cell proliferation was confirmed in vitro. The binding of VEGF-B to its receptor on endothelial cells leads to increased expression and activity of urokinase type plasminogen activator and plasminogen activator inhibitor 1, suggesting a role for VEGF-B in the regulation of extracellular matrix degradation, cell adhesion, and migration. Mouse hearts lacking VEGF-B gene are reduced in size and display vascular dysfunction after coronary occlusion and impaired recovery from experimentally induced myocardial ischemia. These findings reveal a role for VEGF-B in the development or function of coronary vascularure and suggest potential clinical use in therapeutic angiogenesis. Unlike VEGF, the levels of VEGF-B mRNA did not increase significantly under hypoxia. Taken together, the insufficiency of VEGF-B in ischemic myocardium might be account for rar...
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