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Peroxisome proliferator-activated receptor β/δ activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition.
- Source :
-
Hypertension (Dallas, Tex. : 1979) [Hypertension] 2011 Feb; Vol. 57 (2), pp. 223-30. Date of Electronic Publication: 2011 Jan 10. - Publication Year :
- 2011
-
Abstract
- Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is an essential transcription factor in myocardial metabolism. This study aims to investigate the effects of PPARβ/δ 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 PPARβ/δ in adult mice using a tamoxifen-inducible transgenic approach with Cre-LoxP recombination. The expression of PPARβ/δ 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 PPARγ 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 PPARβ/δ in the adult heart improved cardiac function and resisted progression to pathological development in mechanical stress condition. We conclude that PPARβ/δ 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.
- Subjects :
- Animals
Blotting, Western
Carnitine O-Palmitoyltransferase genetics
Carnitine O-Palmitoyltransferase metabolism
Catalase genetics
Catalase metabolism
DNA, Mitochondrial genetics
Gene Expression
Glucose Transporter Type 1 genetics
Glucose Transporter Type 1 metabolism
Glucose Transporter Type 4 genetics
Glucose Transporter Type 4 metabolism
In Vitro Techniques
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria, Heart metabolism
Myocardium pathology
PPAR delta genetics
PPAR-beta genetics
Phosphofructokinases genetics
Phosphofructokinases metabolism
Pressure
Reverse Transcriptase Polymerase Chain Reaction
Stress, Mechanical
Superoxide Dismutase genetics
Superoxide Dismutase metabolism
Heart physiopathology
Mitochondria, Heart physiology
Myocardium metabolism
PPAR delta metabolism
PPAR-beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4563
- Volume :
- 57
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 21220704
- Full Text :
- https://doi.org/10.1161/HYPERTENSIONAHA.110.164590