From the Université Paris Descartes/Paris V, Sorbonne Paris Cité, France (J.M.B.-S.P., G.K., L.G.); Université Pierre et Marie Curie/Paris VI, France (J.M.B.-S.P., G.K.); INSERM, U1138, Paris, France (J.M.B.-S.P., G.K.); Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France (J.M.B.-S.P., G.K.); Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France (J.M.B.-S.P., G.K.); Pôle de Biologie, Hopitâl Européen George Pompidou, AP-HP, Paris, France (G.K.); Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden (G.K.); and Department of Radiation Oncology, Weill Cornell Medical College, New York, NY (L.G.).
Circ Res. 2017 May 26;120(11):1812-1824. doi: 10.1161/CIRCRESAHA.117.311082.
Autophagy contributes to the maintenance of intracellular homeostasis in most cells of cardiovascular origin, including cardiomyocytes, endothelial cells, and arterial smooth muscle cells. Mitophagy is an autophagic response that specifically targets damaged, and hence potentially cytotoxic, mitochondria. As these organelles occupy a critical position in the bioenergetics of the cardiovascular system, mitophagy is particularly important for cardiovascular homeostasis in health and disease. Consistent with this notion, genetic defects in autophagy or mitophagy have been shown to exacerbate the propensity of laboratory animals to spontaneously develop cardiodegenerative disorders. Moreover, pharmacological or genetic maneuvers that alter the autophagic or mitophagic flux have been shown to influence disease outcome in rodent models of several cardiovascular conditions, such as myocardial infarction, various types of cardiomyopathy, and atherosclerosis. In this review, we discuss the intimate connection between autophagy, mitophagy, and cardiovascular disorders.
自噬有助于维持心血管来源的大多数细胞(包括心肌细胞、内皮细胞和动脉平滑肌细胞)的细胞内稳态。线粒体自噬是一种自噬反应,专门针对受损的、因此可能具有细胞毒性的线粒体。由于这些细胞器在心血管系统的生物能量学中占据关键位置,因此线粒体自噬对于心血管在健康和疾病中的稳态特别重要。与这一观点一致的是,已经表明自噬或线粒体自噬的遗传缺陷会加剧实验室动物自发发展心脏退行性疾病的倾向。此外,已经表明,改变自噬或线粒体自噬通量的药理学或遗传学操作会影响几种心血管疾病(如心肌梗死、各种类型的心肌病和动脉粥样硬化)的啮齿动物模型中的疾病结果。在这篇综述中,我们讨论了自噬、线粒体自噬和心血管疾病之间的密切联系。