Lee Weiqian E, Genetzakis Elijah, Figtree Gemma A
Kolling Institute, University of Sydney, Sydney, NSW 2006, Australia.
Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.
Antioxidants (Basel). 2023 Jun 28;12(7):1359. doi: 10.3390/antiox12071359.
Although elevated cholesterol and other recognised cardiovascular risk factors are important in the development of coronary artery disease (CAD) and heart attack, the susceptibility of humans to this fatal process is distinct from other animals. Mitochondrial dysfunction of cells in the arterial wall, particularly the endothelium, has been strongly implicated in the pathogenesis of CAD. In this manuscript, we review the established evidence and mechanisms in detail and explore the potential opportunities arising from analysing mitochondrial function in patient-derived cells such as endothelial colony-forming cells easily cultured from venous blood. We discuss how emerging technology and knowledge may allow us to measure mitochondrial dysfunction as a potential biomarker for diagnosis and risk management. We also discuss the "pros and cons" of animal models of atherosclerosis, and how patient-derived cell models may provide opportunities to develop novel therapies relevant for humans. Finally, we review several targets that potentially alleviate mitochondrial dysfunction working both via direct and indirect mechanisms and evaluate the effect of several classes of compounds in the cardiovascular context.
尽管胆固醇升高和其他公认的心血管危险因素在冠状动脉疾病（CAD）和心脏病发作的发展中很重要，但人类对这一致命过程的易感性与其他动物不同。动脉壁细胞，特别是内皮细胞的线粒体功能障碍，与CAD的发病机制密切相关。在本手稿中，我们详细回顾了已有的证据和机制，并探讨了分析患者来源细胞（如易于从静脉血中培养的内皮集落形成细胞）中线粒体功能所带来的潜在机会。我们讨论了新兴技术和知识如何使我们能够将线粒体功能障碍作为诊断和风险管理的潜在生物标志物进行测量。我们还讨论了动脉粥样硬化动物模型的“利弊”，以及患者来源的细胞模型如何为开发与人类相关的新疗法提供机会。最后，我们回顾了几个可能通过直接和间接机制减轻线粒体功能障碍的靶点，并评估了几类化合物在心血管方面的作用。
