Exercise-induced angiogenesis-related growth and transcription factors in skeletal muscle, and their modification in muscle pathology

Angiogenesis is the process of formation of new blood vessels; it is genera lly a rare occurrence in the adult, although it is a common adaptive respon se to exercise training in skeletal muscle. Current thinking is that angiog enesis is mediated by diffusible angiogenic factors and that the angiogenic activity is regulated through the balance between stimulatory and inhibito ry factors. Recent studies have shown that up-regulation of angiogenic fact ors occurs in response to increased muscle activity in skeletal muscle. The major putative angiogenic factor, vascular endothelial growth factor (VEGF ), seems to increase to a greater extent and more consistently than other m easured angiogenic factors, such as fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (1) (TGF-beta (1)). While the regulating me chanisms in this response are not clear, present data indicate reduced oxyg en tension and/or related metabolic alterations in the skeletal muscle as p ossible stimuli. Data on other angiogenic growth factors are limited, but a n increase in endothelial cell-stimulating angiogenic growth factor (ESAF) has been observed in response to increased blood flow and muscle stretching . Therefore, different exercise associated stimuli may all contribute to ex ercise-induced angiogenesis in skeletal muscle, but possibly through differ ing angiogenic factors and mechanisms. Understanding these processes is imp ortant for the elucidation of mechanisms mediating exercise responsiveness in skeletal muscle, but also for the potential that such understanding migh t bring to the treatment and prevention of human diseases such as intermitt ent claudication.