RAPID INDUCTION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION BY TRANSIENT ISCHEMIA IN RAT-HEART

Vascular endothelial growth factor (VEGF or vascular permeability fact or), a direct-acting, endothelial cell-specific mitogen, has been sugg ested to be involved in development and maintenance of vasculatures in tumor neovascularization and in normal tissues. To investigate possib le roles of VEGF in ischemic hearts, we studied induction of VEGF mRNA by ischemia and hypoxia using coronary artery-ligated hearts in vivo and perfused hearts and cultured myocardial cells in vitro. VEGF mRNA was potently induced by ischemia in the heart in vivo. In perfused hea rts, maximum expression was rapidly induced (within 30 min) by transie nt reversible ischemia (5-10 min of ischemia) and lasted at least 3 h. Induction was also caused by hypoxia, which was confirmed in perfused hearts and cultured myocardial cells. These results suggest that indu ction of VEGF mRNA is upregulated by oxygen deprivation in the heart a nd that not only infarction but also chronic ischemia in the clinical setting could induce VEGF as a potent angiogenesis factor to stimulate coronary collateral formation.