Ablation of the stress protease OMA1 protects against heart failure in mice
- 28 March 2018
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 10 (434)
- https://doi.org/10.1126/scitranslmed.aan4935
Abstract
Heart failure (HF) is a major health and economic burden in developed countries. It has been proposed that the pathogenesis of HF may involve the action of mitochondria. We evaluate three different mouse models of HF: tachycardiomyopathy, HF with preserved left ventricular (LV) ejection fraction (LVEF), and LV myocardial ischemia and hypertrophy. Regardless of whether LVEF is preserved, our results indicate that the three models share common features: an increase in mitochondrial reactive oxygen species followed by ultrastructural alterations in the mitochondrial cristae and loss of mitochondrial integrity that lead to cardiomyocyte death. We show that the ablation of the mitochondrial protease OMA1 averts cardiomyocyte death in all three murine HF models, and thus loss of OMA1 plays a direct role in cardiomyocyte protection. This finding identifies OMA1 as a potential target for preventing the progression of myocardial damage in HF associated with a variety of etiologies.Keywords
Funding Information
- Ministerio de Economía y Competitividad (SAF2012-32776)
- Ministerio de Economía y Competitividad (SAF2015-65633-R)
- Ministerio de Economía y Competitividad (SAF2015-65633-R)
- Ministerio de Economía y Competitividad (SAF2012-32776)
- EU ITN (ITN-GA317433)
- MC-CIG (GA304217)
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