Wang Wei, Wang Xue-Mei, Zhang Hao-Long, Zhao Rui, Wang Yong, Zhang Hao-Ling, Song Zhi-Jing
College of Acupuncture-Moxibustion and Tuina, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China.
College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 73000, Gansu Province, China.
World J Cardiol. 2024 Dec 26;16(12):689-706. doi: 10.4330/wjc.v16.i12.689.
The maintenance of intracellular and extracellular adenosine triphosphate (ATP) levels plays a pivotal role in cardiac function. In recent years, burgeoning attention has been directed towards ATP-induced cell death (AICD), revealing it as a distinct cellular demise pathway triggered by heightened extracellular ATP concentrations, distinguishing it from other forms of cell death such as apoptosis and necrosis. AICD is increasingly acknowledged as a critical mechanism mediating the pathogenesis and progression of various cardiovascular maladies, encompassing myocardial ischemia-reperfusion injury, sepsis-induced cardiomyopathy, hypertrophic cardiomyopathy, arrhythmia, and diabetic cardiomyopathy. Consequently, a comprehensive understanding of the molecular and metabolic underpinnings of AICD in cardiac tissue holds promise for the prevention and amelioration of cardiovascular diseases. This review first elucidates the vital physiological roles of ATP in the cardiovascular system, subsequently delving into the intricate molecular mechanisms and metabolic signatures governing AICD. Furthermore, it addresses the potential therapeutic targets implicated in mitigating AICD for treating cardiovascular diseases, while also delineating the current constraints and future avenues for these innovative therapeutic targets, thereby furnishing novel insights and strategies for the prevention and management of cardiovascular disorders.
细胞内和细胞外三磷酸腺苷(ATP)水平的维持在心脏功能中起着关键作用。近年来,人们越来越关注ATP诱导的细胞死亡(AICD),发现它是一种由细胞外ATP浓度升高触发的独特细胞死亡途径,与细胞凋亡和坏死等其他形式的细胞死亡不同。AICD越来越被认为是介导各种心血管疾病发病机制和进展的关键机制,包括心肌缺血-再灌注损伤、脓毒症诱导的心肌病、肥厚型心肌病、心律失常和糖尿病心肌病。因此,全面了解心脏组织中AICD的分子和代谢基础有望预防和改善心血管疾病。本综述首先阐明了ATP在心血管系统中的重要生理作用,随后深入探讨了控制AICD的复杂分子机制和代谢特征。此外,它还探讨了减轻AICD以治疗心血管疾病的潜在治疗靶点,同时也描述了这些创新治疗靶点目前的局限性和未来的发展方向,从而为心血管疾病的预防和管理提供新的见解和策略。