Molecular biology of the coronary vascular and myocardial responses to ischemia.
To understand the complex mechanism(s) involved in molecular responses to ischemia, we developed two experimental models in pigs. In a "stunning" model of repetitive ischemia and reperfusion, we studied the mRNA expression of immediate early genes like c-fos, c-myc and heat shock protein-70 (HSP-70). Myocardial stunning was achieved by two cycles of 10-min left anterior descending coronary artery (LAD) occlusion and 30 min reperfusion. We observed several-fold enhanced expression of c-fos and HSP-70 mRNA in the stunned myocardium as compared with the control, whereas c-myc mRNA levels remained almost unchanged. In the second model, we examined the expression of the peptide mitogens heparin-binding growth factor 1 (HBGF-1) and transforming growth factor beta 1 (TGF-beta 1) after a chronic coronary artery occlusion leading to myocardial collateralization. Progredient stenosis of the circumflex coronary artery was induced by implanting a hygroscopic ameroid constrictor ring around it and occlusion was verified by in vivo angiography. Using polymerase chain reaction (PCR) and Northern hybridization techniques, we observed significantly enhanced expression of HBGF-1 and TGF-beta 1 in collateralized myocardium as compared with normal. In situ techniques revealed the localization of HBGF-1 transcripts in the blood vessel wall, and TGF-beta 1 in cardiac myocytes and Purkinje cells. Our results clearly indicate that myocardial stunning stimulates the expression of transcription factors which might be involved in regulation of certain growth factors like HBGF-1 and TGF-beta 1 which may play a significant role in the development of a collateral circulation.
Sharma
H S
HS
Department of Experimental Cardiology, Max-Planck Institute, Bad Nauheim, Germany.
Wünsch
M
M
Brand
T
T
Verdouw
P D
PD
Schaper
W
W
D000818:Animals; D015152:Blotting, Northern; D003327:Coronary Disease / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004195:Disease Models, Animal; D016220:Fibroblast Growth Factor 1 / Q000235:genetics; D015870:Gene Expression; D016762:Genes, fos; D016259:Genes, myc; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013552:Swine; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016220:Fibroblast Growth Factor 1