PDF(Pubmed)
Abstract：
Necroptosis, which is distinct from apoptosis and necrosis, serves a crucial role in ontogeny and the maintenance of homeostasis. In the last decade, it has been demonstrated that the pathogenesis of cardiovascular diseases is also linked to necroptosis. Receptor interaction protein kinase (RIPK) 1, RIPK3 and mixed lineage kinase domain‑like protein serve vital roles in necroptosis. In addition to the aforementioned necroptosis‑related components, calcium/calmodulin‑dependent protein kinase II (CaMKII) has been identified as a novel substrate for RIPK3 that promotes the opening of the mitochondrial permeability transition pore (mPTP), and thus, mediates necroptosis of myocardial cells through the RIPK3‑CaMKII‑mPTP signaling pathway. The present review provides an overview of the current knowledge of the RIPK3‑CaMKII‑mPTP‑mediated necroptosis signaling pathway in cardiovascular diseases, focusing on the role of the RIPK3‑CaMKII‑mPTP signaling pathway in acute myocardial infarction, ischemia‑reperfusion injury, heart failure, abdominal aortic aneurysm, atherosclerosis, diabetic cardiomyopathy, hypertrophic cardiomyopathy, atrial fibrillation, and the cardiotoxicity associated with antitumor drugs and other chemicals. Finally, the present review discusses the research status of drugs targeting the RIPK3‑CaMKII‑mPTP signaling pathway.
摘要：
坏死,它不同于细胞凋亡和坏死，在个体发育和维持体内平衡中起着至关重要的作用。在过去的十年里，已经证明，心血管疾病的发病机制也与坏死有关。受体相互作用蛋白激酶（RIPK）1，RIPK3和混合谱系激酶结构域样蛋白在坏死性凋亡中起着至关重要的作用。除了上述与坏死相关的成分外，钙/钙调蛋白依赖性蛋白激酶II（CaMKII）已被确定为RIPK3的新型底物，可促进线粒体通透性转换孔（mPTP）的开放，因此，通过RIPK3-CaMKII-mPTP信号通路介导心肌细胞坏死。本综述概述了心血管疾病中RIPK3-CaMKII-mPTP介导的坏死凋亡信号通路的最新知识，关注RIPK3-CaMKII-mPTP信号通路在急性心肌梗死中的作用，缺血再灌注损伤，心力衰竭,腹主动脉瘤,动脉粥样硬化,糖尿病性心肌病,肥厚型心肌病,心房颤动,以及与抗肿瘤药物和其他化学物质相关的心脏毒性。最后,本文综述了RIPK3-CaMKII-mPTP信号通路靶向药物的研究现状。
