Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy.
Chronic hypobaric hypoxia (CHH) increases load on the right ventricle (RV) resulting in RV hypertrophy. We hypothesized that CHH elicits distinct responses, i.e., the hypertrophied RV, unlike the left ventricle (LV), displaying enhanced mitochondrial respiratory and contractile function. Wistar rats were exposed to 4 weeks CHH (11% O(2)) versus normoxic controls. RV/body weight ratio increased (P < 0.001 vs. control) while RV systolic and developed pressures were higher. However, LV systolic and developed pressures were significantly reduced. Mitochondrial O(2) consumption was sustained in the hypertrophied RV, ADP/O increased (P < 0.01 vs. control) and proton leak significantly decreased. Conversely, LV mitochondrial O(2) consumption was attenuated (P < 0.05 vs. control) and proton leak significantly increased. In parallel, expression of mitochondrial regulators was upregulated in the hypertrophied RV but not the LV. Our data show that the hypertrophied RV induces expression of mitochondrial regulatory genes linking respiratory capacity and enhanced efficiency to sustained contractile function.
Zungu
Makhosazane
M
Hatter Heart Research Institute, Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
Young
Martin E
ME
Stanley
William C
WC
Essop
M Faadiel
MF
D000818:Animals; D019069:Cell Respiration / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D006334:Heart Function Tests; D006439:Hemodynamics; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009200:Myocardial Contraction / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger