Rapid induction of vascular endothelial growth factor expression by transient ischemia in rat heart.
Vascular endothelial growth factor (VEGF or vascular permeability factor), a direct-acting, endothelial cell-specific mitogen, has been suggested to be involved in development and maintenance of vasculatures in tumor neovascularization and in normal tissues. To investigate possible 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 hearts, maximum expression was rapidly induced (within 30 min) by transient 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 induction of VEGF mRNA is upregulated by oxygen deprivation in the heart and 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.
Fourth Department of Internal Medicine, School of Medicine, University of Tokyo, Japan.
E
E
Hashimoto
T
T
Ogita
T
T
Nakaoka
R
R
Matsuoka
A
A
Takao
Y
Y
Kira
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013779:Tetrodotoxin; D003513:Cycloheximide