The protective role of peroxisome proliferator-activated receptor γ coactivator-1α in hyperthyroid cardiac hypertrophy

Heart failure is a major cause of death throughout the world. Hyperthyroidism has been shown to induce cardiac hypertrophy, which is a contributing factor to heart failure. However, the mechanism underling effect of thyroid hormone is not completely clear. The present study investigates the role of peroxisome proliferator-activated receptor (PPAR) ? coactivator-1a (PGC-1a) in cardiac hypertrophy induced by Triiodothyronine (T3). We investigated PGC-1a mRNA expression in rat hearts exposed to T3 in vivo and ex vivo. Surprisingly, we found that the extended periods of T3 treatment led to an increase in PGC-1a expression compared to shorter treatment times, which resulted in a reduction of PGC-1a expression. Mechanistic studies showed that suppression of PGC-1a by small interfering RNA in cardiomyocytes amplified the cellular hypertrophic response to T3 stimulation, whereas overexpression of PGC-1a was protective. Furthermore, we presented evidence to show that T3 decreased PGC-1a expression via p38 mitogen-activated protein kinases (MAPK) pathway. Our studies also revealed that overexpression of PGC-1a in cardiomyocytes inhibited basal and T3-induced p38 MAPK phosphorylation. These data indicate for the first time that PGC-1a plays protective role in T3-induced cardiac hypertrophy and that hypertrophic growth induced by T3 involves a regulatory pathway between PGC-1a and p38 MAPK. J. Cell. Physiol. 227: 32433253, 2012. (C) 2012 Wiley Periodicals, Inc.