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Publication : Peroxisome proliferator-activated receptor β/δ activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition.

First Author  Liu J Year  2011
Journal  Hypertension Volume  57
Issue  2 Pages  223-30
PubMed ID  21220704 Mgi Jnum  J:341447
Mgi Id  MGI:7539605 Doi  10.1161/HYPERTENSIONAHA.110.164590
Citation  Liu J, et al. (2011) Peroxisome proliferator-activated receptor beta/delta activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition. Hypertension 57(2):223-30
abstractText  Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is an essential transcription factor in myocardial metabolism. This study aims to investigate the effects of PPARbeta/delta activation in the adult heart on mitochondrial biology and oxidative metabolism under normal and pressure-overload conditions. We have investigated the effects of cardiac constitutively active PPARbeta/delta in adult mice using a tamoxifen-inducible transgenic approach with Cre-LoxP recombination. The expression of PPARbeta/delta mRNA and protein in cardiomyocytes of adult mice was substantially increased after short-term induction. In these mice, the cardiac expression of key factors involved in mitochondrial biogenesis, such as PPARgamma coactivator-1, endogenous antioxidants Cu/Zn superoxide dismutase, and catalase, fatty acid, and glucose metabolism, such as carnitine palmitoyltransferase Ib, carnitine palmitoyltransferase II, and glucose transporter 4, were upregulated. Subsequently, myocardial oxidative metabolism was elevated concomitant with an increased mitochondrial DNA copy number and an enhanced cardiac performance. Moreover, activation of PPARbeta/delta in the adult heart improved cardiac function and resisted progression to pathological development in mechanical stress condition. We conclude that PPARbeta/delta activation in the adult heart will promote cardiac performance along with transcriptional upregulation of mitochondrial biogenesis and defense, as well as oxidative metabolism at basal and pressure-overload conditions.
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