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.

摘要

简介：先天免疫和适应性免疫在动脉粥样硬化的潜在病理机制中起着关键作用，无菌炎症的潜在靶点为开发新疗法提供了机会。响应内膜层中氧化的 LDL，T 细胞亚群在动脉粥样硬化部位被募集和激活，以上调促动脉粥样硬化的细胞因子，从而加剧斑块形成的不稳定性。

涵盖的领域：在 2001 年 1 月至 2020 年 9 月期间对 PubMed 和 Web of Science 进行了系统搜索，并对无菌炎症和动脉粥样硬化的相关文章进行了严格审查。原始信息是关于危险相关分子模式 (DAMP) 作为无菌炎症的介质与 CD36-TLR4-TLR6 受体复合物之间的相互联系收集的，该受体复合物在动脉粥样硬化的病理生理学中引发和激活炎症小体。无菌炎症的介质被确定为针对动脉粥样硬化管理的治疗策略。

专家意见：通过 NLRP3 炎症小体引起的无菌炎症因 IL-1β 和 IL-18 的激活以及细胞焦亡的诱导而持续，导致释放额外的炎性细胞因子和 DAMP。当前 NLRP3 炎症小体抑制剂的挑战在于靶向 NLRP3 炎症小体成分的特异性、稳定性和有效性，而不改善生存所需的上游或下游反应。