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PPARγ‐Independent Side Effects of Thiazolidinediones on Mitochondrial Redox State in Rat Isolated Hearts
Author(s) -
Salzman Michele,
Cheng Qunli,
Weihrauch Dorothee,
Camara Amadou,
Stowe David,
Riess Matthias
Publication year - 2015
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.29.1_supplement.979.2
Subject(s) - rosiglitazone , pioglitazone , peroxisome proliferator activated receptor , antagonist , mitochondrion , pharmacology , cardiac function curve , ischemia , redox , receptor , medicine , reperfusion injury , endocrinology , heart failure , chemistry , biochemistry , diabetes mellitus , type 2 diabetes , organic chemistry
The effect of anti‐diabetic thiazolidinediones (TZDs) on contributing to heart failure and cardiac ischemia/reperfusion (IR) injury is controversial. Peroxisome proliferator‐activated receptor‐gamma (PPARγ) agonists are under scrutiny because of concerns about their cardiovascular safety. Acute administration of rosiglitazone, for example, was reported to differentially aggravate IR injury in a consomic rat heart model. In this study we investigated the effect of select TZDs on mitochondrial function in rat isolated hearts. Different concentrations of the TZDs rosiglitazone and pioglitazone were administered in the presence or absence of the specific PPARγ antagonist GW9662, and their effects on mitochondrial redox state were measured by online NADH and FAD autofluorescence. Both TZDs resulted in dose‐dependent, reversible increases in mitochondrial oxidation that were not attenuated by GW9662. Taken together, these data suggest excessive mitochondrial uncoupling by a PPARγ‐independent mechanism. If translated clinically, this may explain in part how TZDs adversely enhance cardiac IR injury and adverse events in susceptible patients. Supported by Department of Veterans Affairs (CARA‐026‐10F), NIH and institutional funds.