Xia Peng, Liu Yuening, Cheng Zhaokang
Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, PBS 323, 205 E. Spokane Falls Blvd., P.O. Box 1495, Spokane, WA 99210-1495, USA.
Biomed Res Int. 2016;2016:9583268. doi: 10.1155/2016/9583268. Epub 2016 Dec 22.
Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation.
心血管疾病是全球头号死因,常与心肌细胞的凋亡性死亡相关。由于心肌细胞凋亡是一个高度受调控的过程,对凋亡途径进行药物干预可能是治疗多种心血管疾病和病症(包括心肌梗死、缺血/再灌注损伤、化疗心脏毒性和终末期心力衰竭)的一种有前景的治疗策略。尽管我们对凋亡信号通路的认识迅速增长,但目前尚无针对这一细胞过程的临床适用治疗方法。为了帮助确定未来研究的潜在创新方向,有必要全面了解目前已知在心肌细胞中起作用的凋亡途径。在此,我们总结了多种信号分子和途径对心肌细胞凋亡调控的最新进展,重点关注这些途径在心脏病发病机制中的作用。此外,我们提供了这一知识从实验室到临床转化的最新情况,并讨论了需要进一步研究的未解决问题。