Activation of peroxisome proliferator-activated receptor-α protects the heart from ischemia/reperfusion injury

Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is expressed in the heart and regulates genes involved in myocardial fatty acid oxidation (FAO). The role of PPAR-alpha in acute ischemia/reperfusion myocardial injury remains unclear. The coronary arteries of male mice were ligated for 3...

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Veröffentlicht in:	Circulation (New York, N.Y.) N.Y.), 2003-11, Vol.108 (19), p.2393-2399
Hauptverfasser:	YUE, Tian-Li, WEIKE BAO, MIRABILE, Rosanna C, ARAVINDHAN, Karpagam, OHLSTEIN, Eliot H, JUCKER, Beat M, GU, Juan-Li, ROMANIC, Anne M, BROWN, Peter J, JIANQI CUI, THUDIUM, Douglas T, BOYCE, Rogely, BURNS-KURTIS, Cynthia L
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Blood and lymphatic vessels Butyrates - administration & dosage Butyrates - therapeutic use Cardiology. Vascular system Chemotaxis, Leukocyte - drug effects Cytokines - secretion Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Down-Regulation - drug effects Drug Evaluation, Preclinical Fatty Acids - blood I-kappa B Proteins - biosynthesis Ligation Male Matrix Metalloproteinases - biosynthesis Medical sciences Mice Mice, Knockout Myocardial Infarction - drug therapy Myocardial Infarction - pathology Myocardial Ischemia - drug therapy Myocardial Ischemia - pathology Myocardial Reperfusion Injury - pathology Myocardial Reperfusion Injury - prevention & control Myocardium - enzymology NF-kappa B - antagonists & inhibitors NF-KappaB Inhibitor alpha Oxidation-Reduction Phenylurea Compounds - administration & dosage Phenylurea Compounds - therapeutic use Premedication Receptors, Cytoplasmic and Nuclear - agonists Receptors, Cytoplasmic and Nuclear - deficiency Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - physiology RNA, Messenger - biosynthesis Transcription Factors - agonists Transcription Factors - deficiency Transcription Factors - genetics Transcription Factors - physiology
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Zusammenfassung:	Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is expressed in the heart and regulates genes involved in myocardial fatty acid oxidation (FAO). The role of PPAR-alpha in acute ischemia/reperfusion myocardial injury remains unclear. The coronary arteries of male mice were ligated for 30 minutes. After reperfusion for 24 hours, ischemic and infarct sizes were determined. A highly selective and potent PPAR-alpha agonist, GW7647, was administered by mouth for 2 days, and the third dose was given 1 hour before ischemia. GW7647 at 1 and 3 mg x kg(-1) x d(-1) reduced infarct size by 28% and 35%, respectively (P
ISSN:	0009-7322 1524-4539
DOI:	10.1161/01.CIR.0000093187.42015.6C