Uchikado Yoshihiro, Ikeda Yoshiyuki, Ohishi Mitsuru
Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences Kagoshima University, Kagoshima, Japan.
Front Cardiovasc Med. 2022 May 18;9:905072. doi: 10.3389/fcvm.2022.905072. eCollection 2022.
The heart is dependent on ATP production in mitochondria, which is closely associated with cardiovascular disease because of the oxidative stress produced by mitochondria. Mitochondria are highly dynamic organelles that constantly change their morphology to elongated (fusion) or small and spherical (fission). These mitochondrial dynamics are regulated by various small GTPases, Drp1, Fis1, Mitofusin, and Opa1. Mitochondrial fission and fusion are essential to maintain a balance between mitochondrial biogenesis and mitochondrial turnover. Recent studies have demonstrated that mitochondrial dynamics play a crucial role in the development of cardiovascular diseases and senescence. Disruptions in mitochondrial dynamics affect mitochondrial dysfunction and cardiomyocyte survival leading to cardiac ischemia/reperfusion injury, cardiomyopathy, and heart failure. Mitochondrial dynamics and reactive oxygen species production have been associated with endothelial dysfunction, which in turn causes the development of atherosclerosis, hypertension, and even pulmonary hypertension, including pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Here, we review the association between cardiovascular diseases and mitochondrial dynamics, which may represent a potential therapeutic target.
心脏依赖于线粒体中ATP的产生，由于线粒体产生的氧化应激，这与心血管疾病密切相关。线粒体是高度动态的细胞器，其形态不断变化为细长状（融合）或小的球状（分裂）。这些线粒体动力学受各种小GTP酶、动力相关蛋白1（Drp1）、线粒体分裂蛋白1（Fis1）、线粒体融合蛋白（Mitofusin）和视神经萎缩蛋白1（Opa1）调节。线粒体分裂和融合对于维持线粒体生物发生和线粒体更新之间的平衡至关重要。最近的研究表明，线粒体动力学在心血管疾病的发展和衰老过程中起着关键作用。线粒体动力学的破坏会影响线粒体功能障碍和心肌细胞存活，导致心脏缺血/再灌注损伤、心肌病和心力衰竭。线粒体动力学和活性氧的产生与内皮功能障碍有关，进而导致动脉粥样硬化、高血压甚至肺动脉高压（包括肺动脉高压和慢性血栓栓塞性肺动脉高压）的发展。在此，我们综述心血管疾病与线粒体动力学之间的关联，这可能代表一个潜在的治疗靶点。
