Cardiac dysfunction in mice lacking cytochrome-c oxidase subunit VIaH.
Cytochrome-c oxidase subunit VIaH (COXVIaH) has been implicated in the modulation of COX activity. A gene-targeting strategy was undertaken to generate mice that lacked COXVIaH to determine its role in regulation of oxidative energy production and mechanical performance in cardiac muscle. Total COX activity was decreased in hearts from mutant mice, which appears to be a consequence of altered assembly of the holoenzyme COX. However, total myocardial ATP was not significantly different in wild-type and mutant mice. Myocardial performance was examined using the isolated working heart preparation. As left atrial filling pressure increased, hearts from mutant mice were unable to generate equivalent stroke work compared with hearts from wild-type mice. Direct measurement of left ventricular end-diastolic volume using magnetic resonance imaging revealed that cardiac dysfunction was a consequence of impaired ventricular filling or diastolic dysfunction. These findings suggest that a genetic deficiency of COXVIaH has a measurable impact on myocardial diastolic performance despite the presence of normal cellular ATP levels.
Radford
Nina B
NB
The Cooper Clinic, Dallas, Texas 75230, USA.
Wan
Bang
B
Richman
Angela
A
Szczepaniak
Lidia S
LS
Li
Jia-Ling
JL
Li
Kang
K
Pfeiffer
Kathy
K
Schägger
Hermann
H
Garry
Daniel J
DJ
Moreadith
Randall W
RW
D000818:Animals; D003971:Diastole / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000235:genetics*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D028361:Mitochondrial Diseases / Q000235:genetics*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D010085:Oxidative Phosphorylation; D016277:Ventricular Function, Left
D003576:Electron Transport Complex IV