P2X7: An Untapped Target for the Management of Cardiovascular Disease.

P2X7: An Untapped Target for the Management of Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2020 Oct 01;:ATVBAHA120315116 Authors: Shokoples BG, Paradis P, Schiffrin EL Abstract Chronic low-grade inflammation contributes to the development of several diseases, including cardiovascular disease. Adequate strategies to target inflammation in cardiovascular disease are in their infancy and remain an avenue of great interest. The purinergic receptor P2X7 is a ubiquitously expressed receptor that predominately mediates inflammation and cellular death. P2X7 is a ligand-gated cation channel that is activated in response to high concentrations of extracellular ATP, triggering the assembly and activation of the NLRP3 (nuclear oligomerization domain like receptor family pyrin domain containing 3) inflammasome and subsequent release of proinflammatory cytokines IL (interleukin)-1β and IL-18. Increased P2X7 activation and IL-1β and IL-18 concentrations have been implicated in the development of many cardiovascular conditions including hypertension, atherosclerosis, ischemia/reperfusion injury, and heart failure. P2X7 receptor KO (knockout) mice exhibit a significant attenuation of the inflammatory response, which corresponds with reduced disease severity. P2X7 antagonism blunts blood pressure elevation in hypertension and progression of atherosclerosis in animal models. IL-1β and IL-18 inhibition has shown efficacy in clinical trials...
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research