Title: Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy Authors
|Makhosazane, Zungu -|
|Young, Martin -|
|Stanley, William -|
|Essop, M -|
Submitted to: Molecular and Cellular Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 1, 2008
Publication Date: November 1, 2008
Citation: Makhosazane, Z., Young, M.E., Stanley, W.C., Essop, M.F. 2008. Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy. Molecular and Cellular Biochemistry. 318(1-2):175-181. Interpretive Summary: An inability of the heart to pump enough blood is termed heart failure. One possible explanation for heart failure is that the heart is not able to generate enough energy. Problems with fatty acid metabolism have been suggested. This study investigated whether genes known to be critical for energy metabolism are altered in an animal model of heart disease. The data show that during the early stages of heart disease, the heart attempts to adapt metabolically, in order to maintain energy production. The implications are that a failure to maintain activation of these adaptation processes may trigger energy insufficiency, and therefore contractile dysfunction.
Technical Abstract: 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.