Mitochondrial Proteome Of The Pressure-Overload Hypertrophied Rat Heart

Cardiac hypertrophy induced by prolonged hemodynamic overload, leads to changes in myocardial energy metabolism including an acceleration of glycolysis and limitation in oxidation of long-chain fatty acids and pyruvate. The current study tested the hypothesis that alterations in expression of mitochondrial proteins account for defective oxidative metabolism in hypertrophied hearts. Compensated cardiac hypertrophy was produced in rats by aortic constriction and the mitochondrial proteome was quantitated using amine-reactive, isobaric tagging (iTRAQ®) reagents and tandem mass spectrometry. 250–300 proteins were identified; the largest functional groups being those involved in electron transport (50%), fatty acid metabolism (21%), the TCA cycle (14%) and amino acid metabolism (13%). The expression of 15 mitochondrial proteins was significantly increased in hypertrophied hearts. Among the proteins up-regulated in response to hypertrophy were several involved in mediating or responding to oxidative stress. It is concluded that changes in expression of metabolic proteins do not directly account for alterations in substrate utilization in non-failing hypertrophied hearts. Oxidative stress, induced by pressure overload, may be an important mediator of metabolic adaptation to pressure-overload hypertrophy. Studies were supported by grants from the Canadian Institutes for Health Research.