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Inhibiting mitochondrial uncoupling protein 2 exacerbates myocardial ischemia/reperfusion injury
Author(s) -
Moukdar Fatiha,
Sloan Ruben C.,
Frasier Chad R.,
Brown David A.,
Lust Robert M.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1033.21
Subject(s) - cardioprotection , genipin , ischemia , cardiology , reperfusion injury , medicine , oxidative stress , pharmacology , chemistry , biochemistry , chitosan
Uncoupling protein (UCP) 2 is an inner mitochondrial membrane protein known to mildly dissipate the mitochondrial membrane potential and is expressed in several mammalian tissues, including the heart. When overexpressed, UCP2 has been shown to reduce oxidative stress‐induced death in cultured cardiomyocytes, and cerebral damage in experimental ischemic stroke models. To test the hypothesis that UCP2 is an essential element of the cardiac response to ischemia/reperfusion (I/R) injury, we used hearts from Sprague‐Dawley rats and subjected them to 25 min global ischemia (Langendorff model) followed by 60 min reperfusion with or without the UCP2 inhibitor, genipin. Hearts were instrumented to measure left ventricular (LV) systolic, end‐diastolic, developed pressures (DP), and coronary flow. In genipin treated group, the drug was administered in the perfusate for 20 min before ischemia. Our results show that the inhibition of UCP2 was associated with increased infarct size (81.95 ± 1.994% of the area at risk vs . 34.08 ± 1.771%, p<0.001 ), and decreased post‐ischemic recovery of both LVDP (7.9 ± 1.602% vs . 26.08 ± 1.215%, p<0.001 ), and coronary flow (35.36 ± 3.270% vs . 62.76 ± 4.340%, p<0.01 ). All values are expressed in percent of baseline and compare genipin treated group to control. Our data suggest that UCP2 participates in cardioprotection from IR injury, by limiting necrosis and by promoting functional recovery.