Targeting atherosclerotic inflammation: Advances in NLRP3 inflammasome inhibitors beyond LDL-C

Atherosclerosis, the main pathological background of cardiovascular diseases, is not only characterized by lipid metabolism disorders but also chronic inflammation as a major driver of disease progression. As a key regulator of inflammatory immune responses, the NLRP3 inflamma-some is involved in the development and instability of atherosclerotic plaques. Although reducing low-density lipoprotein cholesterol (LDL-C) confers benefits, residual cardiovascular risk persists, necessitating novel anti-inflammatory therapies. This review provides a comprehensive overview of NLRP3 inflammasome activation mechanisms and its role in plaque inflammation. We systematically summarize current NLRP3 inhibitors under preclinical and clinical development, including small molecules and biologics, with emphasis on design strategies, structural characteristics and pharmacological activities. Challenges in clinical translation, such as tissue targeting and safety, are also discussed. By integrating recent advances in molecular mechanisms and medicinal chemistry, this article aims to provide a theoretical basis for targeted anti-inflammatory therapies beyond lipid lowering.