Atherosclerosis is a chronic process that can culminate with plaque rupture and atherothrombosis. (1) Pro-inflammatory lipoproteins in the lumen of the arteries promote endothelial dysfunction and permeability, leading to accumulations of lipids and migration of pro-inflammatory cells (leukocytes) in the intima of the vessel. (2) Over time, the accumulation of lipids, including cholesterol, and inflammatory cells leads to production of cytokines, including IL-1α, NLRP3 inflammasome activation, and production of inflammasome dependent cytokines IL-1β and IL-18. This process perpetuates endothelial dysfunction, impairs vasodilation, activates leukocytes and promotes oxidative stress, plaque growth and arterial expansive (outward) remodeling. (3) IL-1 activity increases coagulation factors, contributes to platelet activation and promotes plaque rupture and thrombosis. IIllustration credit: Ben Smith
Abbreviations: IL-1α, interleukin-1α; IL-1β, interleukin-1β; IL-18, interleukin-18; NLRP3, NACHT, LRR, and PYD domains-containing protein 3.