Proto-oncogene expression in porcine myocardium subjected to ischemia and reperfusion

T Brand, H S Sharma, K E Fleischmann, D J Duncker, E O McFalls, P D Verdouw, W Schaper
1992 Circulation Research  
The molecular basis of myocardial adaptation to ischemia and reperfusion is poorly understood. It is thought that nuclear proto-oncogenes act as third messengers, converting cytoplasmic signal transduction into long-term changes of gene expression. We studied the expression of six nuclear proto-oncogenes (Egr-1, c-fos, fosB, c-jun, junB, and c-myc) in myocardium subjected to ischemia and reperfusion in anesthetized pigs. Stunning was achieved by two 10-minute left anterior descending coronary
more » ... scending coronary artery occlusions separated by 30 minutes of reperfusion. Hearts were excised after the first occlusion, after the first reperfusion, and at 30, 120, 150, and 210 minutes of reperfusion after the second occlusion. Total RNA was prepared from stunned as well as normally perfused myocardial tissue and subjected to Northern blotting. The response of the six nuclear proto-oncogenes varied.fosB gene expression was never detected. The c-myc gene was expressed, but its level was unchanged by ischemia. c-jun expression was slightly increased by ischemia (3.1±0.6-fold). The c-fos, Egr-1, andjunB genes were highly induced, being fivefold to sevenfold higher in experimental than in control tissue. In three animals pretreated with the f11-antagonist metoprolol and then subjected to the above experimental protocol, the induction of proto-oncogenes was similar to that in nonblocked controls. Our results show that the myocardial adaptive response to ischemic stress includes the induction of at least four transcription factors that may be further operative in repair processes and angiogenesis. (Circulation Research 1992;
doi:10.1161/01.res.71.6.1351 pmid:1385005 fatcat:5ksuvognnvadholjpzlpsmhi64