Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction

Non-infarcted myocardium after coronary occlusion undergoes progressive mor phological and functional changes. The purpose of this study was to determi ne whether non-infarcted myocardium exhibits (1) alteration of the substrat e pattern of myocardial metabolism and (2) concomitant changes in the expre ssion of regulatory proteins of glucose and fatty acid metabolism. Myocardi al infarction was induced in rats by ligation of the left coronary artery. One day and eight weeks after coronary occlusion, glucose and palmitate oxi dation were measured. Expression of selected proteins of metabolism were de termined one day to 12 weeks after infarction. One day after coronary occlu sion no difference of glucose and palmitate oxidation was detectable, where as after eight weeks, glucose oxidation was increased (+ 84%, P<0.05) and p almitate oxidation did not change significantly (- 19%, P = 0.07) in infarc t-containing hearts, compared with hearts from sham-operated rats. One day after coronary occlusion, myocardial mRNA expression of the glucose transpo rter GLUT-1 was increased (+ 86%, P<0.05) and the expression of GLUT-4 was decreased (-28%, P<0.05) in surviving myocardium of infarct-containing hear ts. Protein level of GLUT-1 was increased (+81%, P<0.05) and that of GLUT-4 slightly, but not significantly, decreased (-16%, P-NS). mRNA expressions of heart fatty acid binding protein (H-FABP), and of medium chain acyl-CoA dehydrogenase (MCAD), were decreased by 36% (P<0.05) and 35% (P = 0.07), re spectively. Eight weeks after acute infarction, the left ventricle was hype rtrophied and, at this time-point, there was no difference in the expressio n of GLUT-1 and GLUT-4 between infarcted and sham-operated hearts. However, myocardial mRNA and protein content of MCAD were decreased by 30% (P<0.01) and 27% (P<0.05), respectively. In summary, in surviving myocardium, gluco se oxidation was increased eight weeks after coronary occlusion. Concomitan tly, mRNA and protein expression of MCAD were decreased, compatible with a role of altered expression of regulatory proteins of metabolism in post-inf arction modification of myocardial metabolism. (C) 2000 Academic Press.