The Role of Necroptosis in Cardiovascular Disease

Front Pharmacol. 2018 Jul 6;9:721. doi: 10.3389/fphar.2018.00721. eCollection 2018.


A newly discovered mechanism of cell death, programmed necrosis (necroptosis), combines features of both necrosis and apoptosis. Necroptosis is tightly modulated by a series of characteristic signaling pathways. Activating necroptosis by ligands of death receptors requires the kinase activity of receptor-interacting protein 1 (RIP1), which mediates the activation of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) two critical downstream mediators of necroptosis. Recently, different cytokines have been found participating in this mechanism of cell death. Necroptosis has been proposed as an important component to the pathophysiology of heart disease such as vascular atherosclerosis, ischemia-reperfusion injury, myocardial infarction and cardiac remodeling. Targeting necroptosis signaling pathways may provide therapeutic benefit in the treatment of cardiovascular diseases.

Keywords: RIP1/RIP3/MLKL signaling pathway; cardiac remodeling; ischemia-reperfusion injury; necroptosis; vascular atherosclerosis.

Publication types

  • Review