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NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases
Authors:Eleonora Mezzaroma  Antonio Abbate  Stefano Toldo
Institution:1.VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 23298, USA; (E.M.); (A.A.);2.Pharmacotherapy and Outcomes Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA
Abstract:Virtually all types of cardiovascular diseases are associated with pathological activation of the innate immune system. The NACHT, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome is a protein complex that functions as a platform for rapid induction of the inflammatory response to infection or sterile injury. NLRP3 is an intracellular sensor that is sensitive to danger signals, such as ischemia and extracellular or intracellular alarmins during tissue injury. The NLRP3 inflammasome is regulated by the presence of damage-associated molecular patterns and initiates or amplifies inflammatory response through the production of interleukin-1β (IL-1β) and/or IL-18. NLRP3 activation regulates cell survival through the activity of caspase-1 and gasdermin-D. The development of NLRP3 inflammasome inhibitors has opened the possibility to targeting the deleterious effects of NLRP3. Here, we examine the scientific evidence supporting a role for NLRP3 and the effects of inhibitors in cardiovascular diseases.
Keywords:NLRP3  inflammasome  caspase-1  ASC  IL-1  IL-18  cardiovascular disease  ischemia  heart failure  inhibitor
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