Document Detail

Peroxisome proliferator-activated receptor β/δ activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition.
MedLine Citation:
PMID:  21220704     Owner:  NLM     Status:  MEDLINE    
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.
Jian Liu; Peiyong Wang; Jinwen Luo; Yao Huang; Lan He; Huan Yang; Qingbao Li; Sijie Wu; Olga Zhelyabovska; Qinglin Yang
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-10
Journal Detail:
Title:  Hypertension     Volume:  57     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-20     Completed Date:  2011-04-22     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  223-30     Citation Subset:  IM    
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MeSH Terms
Blotting, Western
Carnitine O-Palmitoyltransferase / genetics,  metabolism
Catalase / genetics,  metabolism
DNA, Mitochondrial / genetics
Gene Expression
Glucose Transporter Type 1 / genetics,  metabolism
Glucose Transporter Type 4 / genetics,  metabolism
Heart / physiopathology*
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria, Heart / metabolism,  physiology*
Myocardium / metabolism*,  pathology
PPAR delta / genetics,  metabolism*
PPAR-beta / genetics,  metabolism*
Phosphofructokinases / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stress, Mechanical
Superoxide Dismutase / genetics,  metabolism
Grant Support
1R01HL084456/HL/NHLBI NIH HHS; 1R01HL085499/HL/NHLBI NIH HHS; R01 HL084456/HL/NHLBI NIH HHS; R01 HL084456-04W1/HL/NHLBI NIH HHS; R01 HL084456-05/HL/NHLBI NIH HHS; R01 HL084456-06/HL/NHLBI NIH HHS; R01 HL085499/HL/NHLBI NIH HHS; R01 HL085499-03W1/HL/NHLBI NIH HHS; R01 HL085499-04/HL/NHLBI NIH HHS; R01 HL085499-05/HL/NHLBI NIH HHS; R21 AT003734/AT/NCCAM NIH HHS
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Glucose Transporter Type 1; 0/Glucose Transporter Type 4; 0/PPAR delta; 0/PPAR-beta; 0/Slc2a1 protein, mouse; 0/Slc2a4 protein, mouse; EC; EC Dismutase; EC O-Palmitoyltransferase; EC 2.7.1 -/Phosphofructokinases

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