Wu Jie, Mei Tingjuan, Dong Yang, Zhang Fen, Li Xingxing, Wang Lei
Department of Cardiology, Jinhua People's Hospital, Jinhua, China.
Department of General Medicine, Community Healthcare Center of Lanjiang Street, Lanxi, China.
Pak J Pharm Sci. 2025 May-Jun;38(3):841-852.
Myocardial fibrosis is a central pathological feature of various cardiovascular diseases, including heart failure and hypertension. It involves the activation of cardiac fibroblasts, transforming them into myofibroblasts that secrete pro-fibrotic factors, leading to excessive extracellular matrix deposition and progressive cardiac dysfunction. Mitochondrial dysfunction plays a critical role in the development of myocardial fibrosis, with mitophagy, a selective form of autophagy, essential for maintaining mitochondrial quality by removing damaged mitochondria. This process is vital in mitigating fibrosis progression. Recent studies suggest that pharmacological modulation of mitophagy may offer novel therapeutic strategies for cardiovascular diseases involving fibrosis. This review explores the mechanisms of mitophagy in myocardial fibrosis, highlighting key proteins and molecular pathways involved in fibroblast activation and mitochondrial dysfunction. Additionally, it discusses the therapeutic potential of targeting mitophagy to mitigate myocardial fibrosis, emphasizing the importance of balancing mitophagy modulation. Overall, targeting mitophagy pathways holds promise as a therapeutic approach for managing myocardial fibrosis and improving heart function.
心肌纤维化是包括心力衰竭和高血压在内的各种心血管疾病的核心病理特征。它涉及心脏成纤维细胞的激活，使其转变为分泌促纤维化因子的肌成纤维细胞，导致细胞外基质过度沉积和进行性心脏功能障碍。线粒体功能障碍在心肌纤维化的发展中起关键作用，而线粒体自噬作为一种选择性自噬形式，对于通过清除受损线粒体来维持线粒体质量至关重要。这一过程对于减轻纤维化进展至关重要。最近的研究表明，线粒体自噬的药理学调节可能为涉及纤维化的心血管疾病提供新的治疗策略。本综述探讨了线粒体自噬在心肌纤维化中的机制，强调了参与成纤维细胞激活和线粒体功能障碍的关键蛋白质和分子途径。此外，它还讨论了靶向线粒体自噬以减轻心肌纤维化的治疗潜力，强调了平衡线粒体自噬调节的重要性。总体而言，靶向线粒体自噬途径有望成为治疗心肌纤维化和改善心脏功能的一种治疗方法。
