Author:
Zungu Makhosazane,Alcolea Maria Pilar,García-Palmer Francisco José,Young Martin E.,Essop M. Faadiel
Abstract
We hypothesized the coordinate induction of mitochondrial regulatory genes in the hypertrophied right ventricle to sustain mitochondrial respiratory capacity and contractile function in response to increased load. Wistar rats were exposed to hypobaric hypoxia (11% O2) or normoxia for 2 wk. Cardiac contractile and mitochondrial respiratory function were separately assessed for the right and left ventricles. Transcript levels of several mitochondrial regulators were measured. A robust hypertrophic response was observed in the right (but not left) ventricle in response to hypobaric hypoxia. Mitochondrial O2consumption was increased in the right ventricle, while proton leak was reduced vs. normoxic controls. Citrate synthase activity and mitochondrial DNA content were significantly increased in the hypertrophied right ventricle, suggesting higher mitochondrial number. Transcript levels of nuclear respiratory factor-1, peroxisome proliferator-activated receptor-γ-coactivator-1α, cytochrome oxidase (COX) subunit II, and uncoupling protein-2 (UCP2) were coordinately induced in the hypertrophied right ventricle following hypoxia. UCP3 transcript levels were significantly reduced in the hypertrophied right ventricle vs. normoxic controls. Exposure to chronic hypobaric hypoxia had no significant effects on left ventricular mitochondrial respiration or contractile function. However, COXIV and UCP2 gene expression were increased in the left ventricle in response to chronic hypobaric hypoxia. In summary, we found coordinate induction of several genes regulating mitochondrial function and higher mitochondrial number in a model of physiological right ventricular hypertrophy, linking the efficiency of mitochondrial oxidative phosphorylation and respiratory function to sustained contractile function in response to the increased load.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
20 articles.
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