Ablation of the stress protease OMA1 protects against heart failure in mice

被引:71
作者
Acin-Perez, Rebeca [1 ]
Victoria Lechuga-Vieco, Ana [1 ,2 ]
del Mar Munoz, Maria [1 ]
Nieto-Arellano, Rocio [1 ]
Torroja, Carlos [1 ]
Sanchez-Cabo, Fatima [1 ]
Jimenez, Concepcion [1 ]
Gonzalez-Guerra, Andres [1 ]
Carrascoso, Isabel [1 ]
Beninca, Cristiane [1 ]
Quiros, Pedro M. [3 ,4 ]
Lopez-Otin, Carlos [3 ,4 ]
Maria Castellano, Jose [1 ,5 ]
Ruiz-Cabello, Jesus [1 ,2 ,6 ]
Jesus Jimenez-Borreguero, Luis [1 ,7 ]
Antonio Enriquez, Jose [1 ,8 ]
机构
[1] Ctr Nacl Invest Cardiovasc Carlos III, Madrid 28029, Spain
[2] Ctr Invest Biomed Red Enfermedades Resp CIBERES, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
[3] Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain
[4] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
[5] HM Hosp, Cardiovasc Hosp Univ Monteprincipe, Ctr Integral Enfermedades, Madrid 28660, Spain
[6] Univ Complutense Madrid, Madrid 28606, Spain
[7] Hosp La Princesa, Ctr Invest Biomed Red Enfermedades Cardiovasc CIB, Madrid 28006, Spain
[8] Ctr Invest Biomed Red Fragilidad & Envejecimiento, C Melchor Fernandez Almagro 3, Madrid 28029, Spain
关键词
MITOCHONDRIAL CALCIUM UNIPORTER; OXIDATIVE STRESS; OPA1; GUIDELINES; MEMBRANE; PACKAGE; OBESITY; CELLS;
D O I
10.1126/scitranslmed.aan4935
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页数:14
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