Ablation of the stress protease OMA1 protects against heart failure in mice
| Autor: | Maria del Mar Muñoz, Jesús Ruiz-Cabello, Rebeca Acín-Pérez, José M. Castellano, Carlos Torroja, Luis Jesús Jiménez-Borreguero, José Antonio Enríquez, Isabel Carrascoso, Carlos López-Otín, Pedro M. Quirós, Concepción Jiménez, Rocio Nieto-Arellano, Cristiane Benincá, Fátima Sánchez-Cabo, Ana Victoria Lechuga-Vieco, Andrés González-Guerra |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty medicine.medical_treatment 030204 cardiovascular system & hematology Mitochondrion Muscle hypertrophy Pathogenesis Mitochondrial Proteins 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Myocytes Cardiac chemistry.chemical_classification Heart Failure Reactive oxygen species Protease Ejection fraction business.industry General Medicine Ablation medicine.disease Mitochondria 030104 developmental biology chemistry Heart failure Cardiology Metalloproteases business Reactive Oxygen Species |
| Zdroj: | Science translational medicine. 10(434) |
| ISSN: | 1946-6242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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