Mechanistic roles of the NLRP3–caspase-1 signaling axis in atherosclerosis: pyroptosis, interaction networks, and therapeutic targets

Abstract

Atherosclerosis (AS) is a chronic inflammatory condition marked by lipid and immune cell accumulation in arteries, leading to plaque formation and vascular dysfunction. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and caspase-1 play key roles in AS pathophysiology by regulating inflammation and cell death, with pyroptosis contributing to vascular inflammation, particularly in endothelial cells (ECs), macrophages, and smooth muscle cells. This review analyzes molecular mechanisms of the NLRP3–caspase-1 axis in AS, including interaction networks of reactive oxygen species, mitochondrial dysfunction, endoplasmic reticulum stress, and non-coding RNAs. By synthesizing recent findings, the study assesses pharmacological agents' therapeutic potential for precision intervention and identifies new strategies for improved AS management.