Yu Fengxue, Ryu Dae Gon, Yoon Ki Tae, Liu Hongqun, Lee Samuel S
Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB T2N 2T8, Canada.
Second Hospital of Hebei Medical University, Shijiazhuang 050004, China.
Int J Mol Sci. 2025 Jul 3;26(13):6423. doi: 10.3390/ijms26136423.
Apoptosis is a highly regulated process of programmed cell death and plays a crucial pathogenic role in a variety of conditions including cardiovascular diseases. There are two pathways leading to apoptosis, the intrinsic and extrinsic pathways. In the intrinsic pathway, also known as the mitochondria-mediated pathway, the cell kills itself because it senses cell stress. Mitochondria account for 30% of cardiomyocyte volume, and therefore, the heart is vulnerable to apoptosis. The extrinsic pathway, also known as the death receptor-mediated pathway, is initiated by death receptors, members of the tumor necrosis factor receptor gene superfamily. Excessive apoptosis is involved in cardiac dysfunction in different cardiac conditions, including heart failure, ischemic heart disease, and cirrhotic cardiomyopathy. The last entity is a serious cardiac complication of patients with cirrhosis. To date, there is no effective treatment for cirrhotic cardiomyopathy. The conventional treatments for non-cirrhotic heart failure such as vasodilators are not applicable due to the generalized peripheral vasodilatation in cirrhotic patients. Exploring new approaches for the treatment of cirrhotic cardiomyopathy is therefore of utmost importance. Since apoptosis plays an essential role in the pathogenesis and progression of cardiovascular conditions, anti-apoptotic treatment could potentially prevent/attenuate the development and progression of cardiac diseases. Anti-apoptotic treatment may also apply to cirrhotic cardiomyopathy. The present review summarizes apoptotic mechanisms in different cardiac diseases, including cirrhotic cardiomyopathy, and potential therapies to regulate apoptosis in these conditions.
细胞凋亡是一种高度调控的程序性细胞死亡过程,在包括心血管疾病在内的多种病症中发挥着关键的致病作用。有两条导致细胞凋亡的途径,即内在途径和外在途径。在内在途径(也称为线粒体介导途径)中,细胞因感知到细胞应激而自我毁灭。线粒体占心肌细胞体积的30%,因此,心脏易受细胞凋亡影响。外在途径(也称为死亡受体介导途径)由死亡受体启动,死亡受体是肿瘤坏死因子受体基因超家族的成员。过度的细胞凋亡参与了不同心脏病症中的心脏功能障碍,包括心力衰竭、缺血性心脏病和肝硬化性心肌病。最后一种病症是肝硬化患者的严重心脏并发症。迄今为止,尚无针对肝硬化性心肌病的有效治疗方法。由于肝硬化患者存在全身性外周血管扩张,用于非肝硬化性心力衰竭的传统治疗方法如血管扩张剂并不适用。因此,探索治疗肝硬化性心肌病的新方法至关重要。由于细胞凋亡在心血管病症的发病机制和进展中起着重要作用,抗细胞凋亡治疗可能会预防/减轻心脏疾病的发生和进展。抗细胞凋亡治疗也可能适用于肝硬化性心肌病。本综述总结了不同心脏疾病(包括肝硬化性心肌病)中的细胞凋亡机制以及在这些病症中调节细胞凋亡的潜在疗法。