Pathophysiology
Clinical meaning
Atherosclerosis is a chronic inflammatory disease of medium and large arteries progressing through distinct stages. Initiation occurs at sites of endothelial dysfunction โ branch points, bifurcations, and areas of disturbed laminar flow โ where endothelial cells express adhesion molecules (VCAM-1, ICAM-1, selectins) and become permeable to circulating LDL particles. Subendothelial LDL undergoes oxidative modification by reactive oxygen species, creating oxidized LDL (oxLDL) that is a potent pro-inflammatory stimulus. OxLDL activates endothelial cells to secrete MCP-1 (monocyte chemoattractant protein-1), recruiting circulating monocytes that transmigrate into the intima and differentiate into tissue macrophages. Macrophages express scavenger receptors (SR-A, CD36) that internalize oxLDL without negative feedback regulation, transforming macrophages into lipid-engorged foam cells โ the hallmark of the fatty streak (earliest visible lesion). Foam cells secrete inflammatory cytokines (TNF-alpha, IL-1, IL-6) and matrix metalloproteinases (MMPs) that degrade extracellular matrix, perpetuating a cycle of inflammation and tissue remodeling. As the lesion progresses, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, proliferate, and synthesize collagen and elastin forming a fibrous cap overlying the lipid-rich necrotic core (composed of dead foam cells,...