Myocardial metabolic regulation through peroxisome proliferator-activated receptor alpha after myocardial infarction.
Although peroxisome proliferator-activated receptor alpha (PPARalpha) is closely associated with myocardial fatty acid metabolism, the pathophysiological role of PPARalpha in myocardial infarction (MI) is not yet known. The aim of the present study was to clarify the relationship between cardiac energy metabolism and PPARalpha expression in the remodelling of myocardium after MI. We assayed the expression of PPARalpha and several metabolic genes in cultured cardiac cells (myocytes and nonmyocytes) and in MI hearts. PPARalpha was strongly expressed in cardiac myocytes but not in nonmyocytes (mainly fibroblasts). In MI rats, PPARalpha and PPARalpha-regulated genes (lipoprotein lipase, heart-type fatty acid binding protein, long-chain acyl-CoA dehydrogenase and uncoupling protein-3) were decreased concomitantly, whereas uncoupling protein-2 was not decreased in severely ischemic regions. Immunohistochemical staining for PPARalpha was less decreased in borderline myocardium than in sham-operated hearts. Furthermore, in electron microscopic study, there were no lipid droplet accumulations in surviving myocardium after MI. Our results suggest that the reduced expression of PPARalpha is closely related to that of fatty acid metabolism genes in infarcted myocardium, and PPARalpha may play an important role in cardiac energy metabolism during remodelling after MI.
Masamura
Katsuhiko
K
Third Department of Internal Medicine, Fukui Medical University, Fukui, Japan.
Tanaka
Nobuyoshi
N
Yoshida
Masahiro
M
Kato
Masayuki
M
Kawai
Yasuyuki
Y
Oida
Koji
K
Miyamori
Isamu
I