Koentges Christoph, Bode Christoph, Bugger Heiko
Division of Cardiology and Angiology I, Heart Center Freiburg University , Freiburg , Germany.
Front Cardiovasc Med. 2016 Oct 13;3:38. doi: 10.3389/fcvm.2016.00038. eCollection 2016.
Functional defects in mitochondrial biology causally contribute to various human diseases, including cardiovascular disease. Impairment in oxidative phosphorylation, mitochondrial oxidative stress, and increased opening of the mitochondrial permeability transition pore add to the underlying mechanisms of heart failure or myocardial ischemia-reperfusion (IR) injury. Recent evidence demonstrated that the mitochondrial NAD-dependent deacetylase sirtuin 3 (SIRT3) may regulate these mitochondrial functions by reversible protein lysine deacetylation. Loss of function studies demonstrated a role of impaired SIRT3 activity in the pathogenesis of myocardial IR injury as well as in the development of cardiac hypertrophy and the transition into heart failure. Gain of function studies and treatment approaches increasing mitochondrial NAD availability that ameliorate these cardiac pathologies have led to the proposal that activation of SIRT3 may represent a promising therapeutic strategy to improve mitochondrial derangements in various cardiac pathologies. In the current review, we will present and discuss the available literature on the role of SIRT3 in cardiac physiology and disease.
线粒体生物学功能缺陷是导致包括心血管疾病在内的多种人类疾病的原因之一。氧化磷酸化受损、线粒体氧化应激以及线粒体通透性转换孔开放增加，都是心力衰竭或心肌缺血再灌注（IR）损伤的潜在机制。最近的证据表明，线粒体烟酰胺腺嘌呤二核苷酸（NAD）依赖性去乙酰化酶沉默调节蛋白3（SIRT3）可能通过可逆的蛋白质赖氨酸去乙酰化作用来调节这些线粒体功能。功能丧失研究表明，SIRT3活性受损在心肌IR损伤的发病机制以及心脏肥大的发展和向心力衰竭的转变中起作用。功能获得研究和增加线粒体NAD可用性的治疗方法改善了这些心脏疾病，这表明激活SIRT3可能是改善各种心脏疾病中线粒体紊乱的一种有前景的治疗策略。在本综述中，我们将展示并讨论关于SIRT3在心脏生理学和疾病中的作用的现有文献。
