Cellular and Molecular Cardiovascular Pathophysiology Laboratory, Department of Biology, E and E.S. (DiBEST), University of Calabria, Arcavacata di Rende, 87036, Cosenza, Italy.
Department of Health Science, University Magna Graecia of Catanzaro, 88100, Catanzaro, Italy.
J Transl Med. 2023 Sep 19;21(1):635. doi: 10.1186/s12967-023-04498-5.
A large body of evidence indicates the existence of a complex pathophysiological relationship between cardiovascular diseases and cancer. Mitochondria are crucial organelles whose optimal activity is determined by quality control systems, which regulate critical cellular events, ranging from intermediary metabolism and calcium signaling to mitochondrial dynamics, cell death and mitophagy. Emerging data indicate that impaired mitochondrial quality control drives myocardial dysfunction occurring in several heart diseases, including cardiac hypertrophy, myocardial infarction, ischaemia/reperfusion damage and metabolic cardiomyopathies. On the other hand, diverse human cancers also dysregulate mitochondrial quality control to promote their initiation and progression, suggesting that modulating mitochondrial homeostasis may represent a promising therapeutic strategy both in cardiology and oncology. In this review, first we briefly introduce the physiological mechanisms underlying the mitochondrial quality control system, and then summarize the current understanding about the impact of dysregulated mitochondrial functions in cardiovascular diseases and cancer. We also discuss key mitochondrial mechanisms underlying the increased risk of cardiovascular complications secondary to the main current anticancer strategies, highlighting the potential of strategies aimed at alleviating mitochondrial impairment-related cardiac dysfunction and tumorigenesis. It is hoped that this summary can provide novel insights into precision medicine approaches to reduce cardiovascular and cancer morbidities and mortalities.
大量证据表明,心血管疾病和癌症之间存在复杂的病理生理关系。线粒体是至关重要的细胞器,其最佳活性由质量控制系统决定,这些系统调节着从中间代谢和钙信号到线粒体动力学、细胞死亡和线粒体自噬等关键细胞事件。新出现的数据表明,受损的线粒体质量控制会导致几种心脏病中的心肌功能障碍,包括心肌肥大、心肌梗死、缺血/再灌注损伤和代谢性心肌病。另一方面,不同的人类癌症也会失调线粒体质量控制以促进其起始和进展,这表明调节线粒体动态平衡可能代表一种有前途的治疗策略,既适用于心脏病学,也适用于肿瘤学。在这篇综述中,我们首先简要介绍了线粒体质量控制系统的生理机制,然后总结了目前对失调线粒体功能在心血管疾病和癌症中的影响的认识。我们还讨论了与主要当前抗癌策略相关的心血管并发症风险增加的关键线粒体机制,强调了旨在缓解与线粒体损伤相关的心脏功能障碍和肿瘤发生的策略的潜力。我们希望这篇综述能为减少心血管疾病和癌症发病率和死亡率的精准医学方法提供新的见解。