Role of RIPK3-CaMKII-mPTP signaling pathway-mediated necroptosis in cardiovascular diseases (Review)

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.