Immunological mechanisms underlying sterile inflammation in the pathogenesis of atherosclerosis: potential sites for intervention. (2nd January 2021)

• Record Type: Journal Article
• Authors: Truong, Roland; Thankam, Finosh G.; Agrawal, Devendra K.
• Is Part Of: Expert review of clinical immunology. Volume 17:Number 1(2021)
• Page Start: 37
• Page End: 50
• Publication Date: 2021-01-02
• Subjects: Atherosclerosis -- CD36 -- DAMPs -- HMGB1 -- inflammasomes -- NLRP3 -- oxidized LDL -- pyroptosis -- sterile Inflammation -- toll-like receptors; Clinical immunology -- Periodicals; 616.079
• DOI: 10.1080/1744666X.2020.1860757
• Languages: English
• ISSNs: 1744-666X

Abstract

ABSTRACT: Introduction : Innate and adaptive immunity play a critical role in the underlying pathological mechanisms of atherosclerosis and potential target sites of sterile inflammation open opportunities to develop novel therapeutics. In response to oxidized LDL in the intimal layer, T cell subsets are recruited and activated at the site of atheroma to upregulate pro-atherogenic cytokines which exacerbate plaque formation instability. Areas covered : A systematic search of PubMed and the Web of Science was performed between January 2001- September 2020 and relevant articles in sterile inflammation and atherosclerosis were critically reviewed. The original information was collected on the interconnection between danger associated molecular patterns (DAMPs) as the mediators of sterile inflammation and the receptor complex of CD36-TLR4-TLR6 that primes and activates inflammasomes in the pathophysiology of atherosclerosis. Mediators of sterile inflammation are identified to target therapeutic strategies in the management of atherosclerosis. Expert opinion : Sterile inflammation via NLRP3 inflammasome is perpetuated by the activation of IL-1β and IL-18 and induction of pyroptosis resulting in the release of additional inflammatory cytokines and DAMPs. Challenges with current inhibitors of the NLRP3 inflammasome lie in the specificity, stability, and efficacy in targeting the NLRP3 inflammasome constituents without ameliorating upstream or downstream responses necessary for survival.