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The protective role of peroxisome proliferator-activated receptor gamma coactivator-1alpha in hyperthyroid cardiac hypertrophy.

Authors: Xu, W  Hou, D  Jiang, X  Lu, Z  Guo, T  Liu, Y  Wang, D  Zen, K  Yu, B  Zhang, CY 
Citation: Xu W, etal., J Cell Physiol. 2012 Sep;227(9):3243-53. doi: 10.1002/jcp.24015.
Pubmed: (View Article at PubMed) PMID:22105890
DOI: Full-text: DOI:10.1002/jcp.24015

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) gamma coactivator-1alpha (PGC-1alpha) in cardiac hypertrophy induced by Triiodothyronine (T3). We investigated PGC-1alpha 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-1alpha expression compared to shorter treatment times, which resulted in a reduction of PGC-1alpha expression. Mechanistic studies showed that suppression of PGC-1alpha by small interfering RNA in cardiomyocytes amplified the cellular hypertrophic response to T3 stimulation, whereas overexpression of PGC-1alpha was protective. Furthermore, we presented evidence to show that T3 decreased PGC-1alpha expression via p38 mitogen-activated protein kinases (MAPK) pathway. Our studies also revealed that overexpression of PGC-1alpha in cardiomyocytes inhibited basal and T3-induced p38 MAPK phosphorylation. These data indicate for the first time that PGC-1alpha plays protective role in T3-induced cardiac hypertrophy and that hypertrophic growth induced by T3 involves a regulatory pathway between PGC-1alpha and p38 MAPK.

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CRRD Object Information
CRRD ID: 7242192
Created: 2013-04-01
Species: All species
Last Modified: 2013-04-01
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.