Caspase Recruitment Domain Family Member 8: A Favorable Target in the Pathogenesis of Atherosclerosis

Dandan Tian,Li Liu,Guang-Gui Zeng,Jinrong He,Huiqing Liu,Dandan Ma,Zixin Yang,Xiangyan Ma,Yunxiang Cao,Chun Xu

Published 2026 in Reviews in cardiovascular medicine

ABSTRACT

Atherosclerosis, a lipid-driven chronic inflammatory disease, is the primary pathological basis of cardiovascular diseases, characterized by endothelial injury, lipid deposition, immune cell infiltration, and chronic inflammation. The NOD-like Receptor Pyrin Domain-Containing 3 (NLRP3) inflammasome has emerged as a crucial mediator of inflammation in atherosclerosis, with caspase recruitment domain family member 8 (CARD8) acting as a key regulatory component. Indeed, CARD8, a member of the caspase recruitment domain family, regulates immune responses by modulating inflammasome activity, particularly NLRP3. Recent studies suggest that CARD8 influences various aspects of atherosclerotic development, including lipid accumulation, oxidative stress, vascular inflammation, smooth muscle cell proliferation, and plaque instability. Thus, this review summarizes the latest findings on the role of CARD8 in the pathogenesis of atherosclerosis, with a focus on the regulatory effects of this component on immune cells and inflammatory pathways. We also discuss the potential of targeting CARD8 as a therapeutic strategy for atherosclerosis, exploring the current preclinical and clinical evidence.

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