Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth, Australia; Department of Biotechnology, School of Pharmacy, Mashhad University of Western Australia, Mashhad, Iran.
Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Metabolism. 2023 Sep;146:155659. doi: 10.1016/j.metabol.2023.155659. Epub 2023 Jul 11.
One of the newly recognized types of cell death is ferroptosis which is related to the accumulation of iron and lipid-reactive oxygen species. Ferroptosis is considered a programmed cell death with a different mechanism from apoptosis, necrosis, and autophagy. Emerging evidence suggests that ferroptosis may occur in the context of cardiovascular disease (CVD), cancer, neurodegenerative diseases, and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line therapy for dyslipidemia. The suppression of the HMG-CoA reductase by statins leads to decreased expression of glutathione peroxidase 4 (GPX4), a key regulator of lipid peroxidation, which in turn results in lipid ROS production and induction of ferroptosis. Experimental data suggest that statins may act as anti-cancer drugs by enhancing tumor cells' ferroptosis. In contrast, statins have also been reported to mitigate ferroptosis in animal models of myocardial ischemia-reperfusion and heart failure. This mini-review presents statin effects on the ferroptosis pathway, based on up-to-date in vivo and in vitro research. Furthermore, the potential impact of these effects on cardiometabolic diseases (e.g., CVD and NAFLD) and cancer is briefly discussed. Overall, there is a need for future studies focusing on statin-induced changes in ferroptosis as a therapeutic approach to such diseases.
细胞死亡的一种新类型是铁死亡，它与铁和脂质活性氧物质的积累有关。铁死亡被认为是一种程序性细胞死亡，其机制与细胞凋亡、坏死和自噬不同。新出现的证据表明，铁死亡可能发生在心血管疾病 (CVD)、癌症、神经退行性疾病和非酒精性脂肪性肝病 (NAFLD) 中。他汀类药物是治疗血脂异常的一线药物。他汀类药物抑制 HMG-CoA 还原酶，导致谷胱甘肽过氧化物酶 4 (GPX4) 的表达减少，GPX4 是脂质过氧化的关键调节剂，这反过来又导致脂质 ROS 的产生和铁死亡的诱导。实验数据表明，他汀类药物可能通过增强肿瘤细胞的铁死亡而发挥抗癌作用。相比之下，他汀类药物也被报道可减轻心肌缺血再灌注和心力衰竭动物模型中的铁死亡。本综述根据最新的体内和体外研究，介绍了他汀类药物对铁死亡途径的影响。此外，还简要讨论了这些影响对心脏代谢疾病（如 CVD 和 NAFLD）和癌症的潜在影响。总的来说，需要进一步的研究来关注他汀类药物诱导的铁死亡变化，作为治疗这些疾病的一种方法。
