Targeting the NLRP3 inflammasome to treat cardiovascular fibrosis

Publication date: Available online 22 February 2020Source: Pharmacology & TherapeuticsAuthor(s): Anita A. Pinar, Tara E. Scott, Brooke M. Huuskes, Felipe E. Tapia Cáceres, Barbara K. Kemp-Harper, Chrishan S. SamuelAbstractCardiovascular fibrosis refers to the scar tissue that develops in the injured heart and blood vessels from an aberrant wound healing response to organ injury or insult. Established fibrosis becomes a hallmark of chronic disease progression and a key contributor to tissue stiffness and dysfunction, which ultimately leads to heart failure. As wound healing and fibrotic responses to myocardial injury are multifactorial processes, current therapies that only target specific contributing factors to disease pathogenesis offer limited overall anti-fibrotic efficacy. As such, recent attention has turned to targeting the body’s immune system, which orchestrates the wound healing response to tissue injury. This review focuses on the increasing body of work that has identified the NLRP3 inflammasome, a multiprotein oligomer complex responsible for activation of inflammatory responses via its production of IL-1β and IL-18, as an immune system-initiated facilitator of cardiovascular healing, but also an important contributor to tissue scarring following its persistent activation. The review summarises the factors that can elicit priming and activation of the inflammasome complex, how the activated inflammasome complex contributes to cardiovascular pathophysiology an...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research