Three-Dimensional Perspectives on Inflammatory Regulation in Coronary Atherosclerosis: Integrated Mechanisms of Endothelial Priming, Lipid Metabolism, and Cytokine Synergy

Atherosclerosis, a leading cause of global mortality, is a chronic inflammatory disease driven by a vicious cycle of endothelial dysfunction, dysregulated lipid metabolism, and persistent inflammation. This review examines the mechanisms through which diverse triggers initiate the cycle. We discuss key cellular and molecular events, such as the detrimental phenotypic switching of vascular smooth muscle cells. We also describe the processes through which various upstream signals converge on core inflammatory hubs, such as the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway and the nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. By integrating these established mechanisms with recent findings on novel regulators, including the chemokine hemofiltrate CC chemokine 1 (HCC-1) and cell surface glycoRNA, this review identifies several potential new biomarkers. Overall, this review aimed to provide a comprehensive understanding of the pathogenesis of atherosclerosis, informing future research and the development of targeted interventions.