Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

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Background: Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism.Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy.Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin click here (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy.ATP concentration, ROS level, and myocardial apoptosis were also examined.

A parallel set of experiments was also conducted in UCP2-/- mice.Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular click here weight/thickness and increased size of myocardial cell (vs.sham controls).ATP concentration was decreased; ROS level was increased.

Apoptosis and fibrosis markers were increased.TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels.Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above.Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice.

Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.