Department of Pathophysiology, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russian Federation.
Department of Biochemistry, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russian Federation.
Int J Mol Med. 2021 Jan;47(1):23-36. doi: 10.3892/ijmm.2020.4781. Epub 2020 Nov 4.
The leading cause of death in developed countries is cardiovascular disease, where coronary heart disease is the main cause of death. Myocardial reperfusion is the most significant method to prevent cell death after ischemia. However, restoration of blood flow may paradoxically lead to myocardial ischemia‑reperfusion injury (MI/RI) accompanied by metabolic disturbances and cardiomyocyte death. As the myocardium has an extremely limited ability to regenerate, the mechanisms of regulated cell death, including apoptosis, are the most significant for contemporary research due to their reversibility. BCL2 is a key anti‑apoptotic protein. There are several signaling pathways and compounds regulating BCL2, including PI3K/AKT and MEK1/ERK1/2, JAK2/STAT3, endothelial nitric oxide synthase, PTEN, cardiac ankyrin repeat protein and microRNA, which can serve as targets for modern methods of cardioprotective therapy inhibiting intrinsic apoptosis and saving viable cardiomyocytes after MI/RI. The present review considers the mechanisms of Bcl2‑regulated apoptosis in the development and treatment of MI/RI.
在发达国家，导致死亡的主要原因是心血管疾病，其中冠心病是主要的死亡原因。心肌再灌注是预防缺血后细胞死亡的最主要方法。然而，血流的恢复可能会导致心肌缺血再灌注损伤（MI/RI），伴有代谢紊乱和心肌细胞死亡。由于心肌的再生能力极其有限，因此，包括细胞凋亡在内的调节性细胞死亡机制是当代研究的重点，因为它们具有可逆性。BCL2 是一种关键的抗凋亡蛋白。有几种信号通路和化合物可以调节 BCL2，包括 PI3K/AKT 和 MEK1/ERK1/2、JAK2/STAT3、内皮型一氧化氮合酶、PTEN、心脏锚蛋白重复蛋白和 microRNA，它们可以作为抑制内在细胞凋亡和保存 MI/RI 后存活心肌的现代心脏保护治疗方法的靶点。本综述考虑了 Bcl2 调节的细胞凋亡在 MI/RI 发生和治疗中的机制。
