Ablation of the stress protease OMA1 protects against heart failure in mice
Ablation of the stress protease OMA1 protects against heart failure in mice
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DOI：
10.1126/scitranslmed.aan4935
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发表时间：
2018-03-28
影响因子：
17.1
通讯作者：
Antonio Enriquez, Jose
中科院分区：
文献类型：
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作者：
Acin-Perez, Rebeca;Victoria Lechuga-Vieco, Ana;Antonio Enriquez, Jose
心力衰竭（HF）是发达国家的主要健康和经济负担。有人提出HF的发病机制可能涉及线粒体的作用。我们评估了三种不同的HF小鼠模型：快速型心肌病，HF保留左心室（LV）射血分数（LVEF），和LV心肌缺血和肥大。无论LVEF是否保留，我们的研究结果表明，这三种模型具有共同的特征：线粒体活性氧增加，随后线粒体嵴超微结构改变，线粒体完整性丧失，导致心肌细胞死亡。我们发现，在所有三种小鼠HF模型中，线粒体蛋白酶OMA1的消融可避免心肌细胞死亡，因此OMA1的丢失在心肌细胞保护中起直接作用。这一发现将OMA1确定为预防与各种病因相关的HF中心肌损伤进展的潜在靶点。
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.