Growth factor activation in myocardial vascularization: therapeutic implications.
A rapid growth of the coronary vasculature occurs during prenatal and early postnatal periods as precursor cells from the epi- and sub-epicardium differentiate, migrate and form vascular structures (vasculogenesis) which then fuse, branch and in some cases recruit cells to form three tunics (angiogenesis). These processes are tightly controlled by temporally and spatially expressed growth factors which are stimulated by metabolic and mechanical factors. The process of angiogenesis in the myocardium is not limited to developmental periods of life, but may occur when the heart is challenged by enhanced loading conditions or during hypoxia or ischemia. This review focuses on the activation of growth factors by metabolic and mechanical stimuli in the developing heart and in the adult heart undergoing adaptive responses. Experimental studies support the hypotheses that both metabolic (hypoxia) and mechanical (stretch) factors serve as powerful stimuli for the up-regulation of growth factors which facilitate angiogenesis and arteriogenesis. Both hypoxia and stretch are powerful inducers of VEGF and its receptors, and provide for paracrine and autocrine signaling. In addition to the VEGF family, bFGF and angiopoietins play major roles in myocardial vascularization. Sufficient evidence supports the hypothesis that mechanical (e.g., bradycardia) and metabolic (e.g., thyroxine analogs) may provide effective non-invasive angiogenic therapies for the ischemic and post-infarcted heart.
Tomanek
Robert J
RJ
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA. robert-tomanek@uiowa.edu
Zheng
Wei
W
Yue
Xinping
X
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006133:Growth Substances / Q000378:metabolism*; D006321:Heart / Q000196:embryology / Q000502:physiology*; D006801:Humans; D000860:Hypoxia; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D006133:Growth Substances; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2