Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Mol Med. 2024 Sep;28(18):e70074. doi: 10.1111/jcmm.70074.
Despite extensive progress in the knowledge and understanding of cardiovascular diseases and significant advances in pharmacological treatments and procedural interventions, cardiovascular diseases (CVD) remain the leading cause of death globally. Mitochondrial dynamics refers to the repetitive cycle of fission and fusion of the mitochondrial network. Fission and fusion balance regulate mitochondrial shape and influence physiology, quality and homeostasis. Mitophagy is a process that eliminates aberrant mitochondria. Melatonin (Mel) is a pineal-synthesized hormone with a range of pharmacological properties. Numerous nonclinical trials have demonstrated that Mel provides cardioprotection against ischemia/reperfusion, cardiomyopathies, atherosclerosis and cardiotoxicity. Recently, interest has grown in how mitochondrial dynamics contribute to melatonin cardioprotective effects. This review assesses the literature on the protective effects of Mel against CVD via the regulation of mitochondrial dynamics and mitophagy in both in-vivo and in-vitro studies. The signalling pathways underlying its cardioprotective effects were reviewed. Mel modulated mitochondrial dynamics and mitophagy proteins by upregulation of mitofusin, inhibition of DRP1 and regulation of mitophagy-related proteins. The evidence supports a significant role of Mel in mitochondrial dynamics and mitophagy quality control in CVD.
尽管在心血管疾病的知识和理解方面取得了广泛的进展，以及在药物治疗和程序干预方面取得了重大进展，但心血管疾病（CVD）仍然是全球死亡的主要原因。线粒体动力学是指线粒体网络的裂变和融合的反复循环。裂变和融合平衡调节线粒体的形状并影响生理、质量和动态平衡。自噬是一种消除异常线粒体的过程。褪黑素（Mel）是一种由松果腺合成的激素，具有多种药理学特性。大量的非临床试验已经证明，Mel 对缺血/再灌注、心肌病、动脉粥样硬化和心脏毒性具有心脏保护作用。最近，人们对线粒体动力学如何有助于褪黑素的心脏保护作用产生了兴趣。本综述评估了 Mel 通过调节体内和体外研究中线粒体动力学和自噬来防治 CVD 的文献。还综述了其心脏保护作用的信号通路。Mel 通过上调融合蛋白、抑制 DRP1 和调节自噬相关蛋白来调节线粒体动力学和自噬蛋白。有证据表明，Mel 在 CVD 中线粒体动力学和自噬质量控制中起着重要作用。
