Neovascularization- angiogenesis and arteriogenesis, represents an important element of tissue response to ischemia. A number of growth factors, including FGFs and VEGFs play important roles in regulation of these events. While roles played by VEGFs are being defined, relatively little is known about contributions of specific FGFs or FGFs receptors. The previous grant application focused on the role of nitric oxide (NO) and other molecular events underlying VEGF and FGF2 stimulation of angiogenesis. The purpose of this competitive renewal is to extend the results of our current studies in order to explore new facets of regulation of coronary angiogenesis and to elucidate mechanisms of the observed growth factor effects. The proposed research in this application builds directly on our current studies and will take advantage of novel models and approaches to the study of angiogenesis developed in the course of previous studies. In particular, our primary focus will be on contributions of FGFs (and, in particular, FGF2) and FGF receptors to angiogenic response in physiological and pathological states. We intend to take advantage of recently developed tools to selectively inhibit biological effects of specific FGFs while not affecting signaling of other growth factors. As the result we expect to define contributions of FGFs to ischemia-induced angiogenesis key molecular events involved in angiogenic activity of FGF2 and elucidate contribution of endothelium and circulating endothelial precursor cells to FGF-mediated angiogenesis.
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