Targeting the NLRP3 inflammasome to treat cardiovascular fibrosis

Anita A. Pinar, Tara E. Scott, Brooke M. Huuskes, Felipe E. Tapia Cáceres, Barbara K. Kemp-Harper, Chrishan S. Samuel

Research output: Contribution to journalReview ArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Cardiovascular 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 and fibrosis progression, and the molecular mechanisms involved from various cell culture and animal model studies that have utilised genetic deletion or pharmacological inhibition of specific components of the inflammasome. Finally, it outlines currently known and previously unrecognised cardiovascular receptors that may be pharmacologically targeted to ablate the contribution of the NLRP3 inflammasome to cardiovascular diseases characterised by fibrosis, by compounds that may be developed as effective adjunct therapies to current standard of care medication.

Original languageEnglish
Article number107511
Number of pages22
JournalPharmacology and Therapeutics
Volume209
DOIs
Publication statusPublished - May 2020

Keywords

  • Angiotensin II
  • Cardiovascular disease
  • Fibrosis
  • IL-18
  • IL-1β
  • NLRP3 inflammasome
  • TGF-β1

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