A chronic inflammatory response of the arterial wall, initiated by injury to the endothelium. Scroll down to walk through the seven-stage pathogenesis of plaque formation and rupture.
The process begins with chronic injury to the arterial endothelium. This can be caused by risk factors such as hyperlipidemia, hypertension, smoking, toxins, or hemodynamic shear stress. The injured endothelium becomes increasingly permeable and expresses adhesion molecules.
Due to increased permeability, Low-Density Lipoproteins (LDL) infiltrate the tunica intima — the innermost layer of the artery. Once inside, reactive oxygen species oxidize the LDL. Oxidized LDL (oxLDL) is highly pro-inflammatory and toxic to surrounding cells.
The dysfunctional endothelium secretes chemokines that attract circulating monocytes (white blood cells). These monocytes bind to the adhesion molecules on the endothelial surface and squeeze between the endothelial cells to enter the intimal space.
Once in the intima, monocytes differentiate into macrophages. They use scavenger receptors to engulf the oxidized LDL. As they gorge on lipids, they transform into lipid-laden foam cells. The accumulation of these cells creates the earliest visible lesion: the fatty streak.
Inflammatory cytokines and growth factors released by macrophages and endothelial cells stimulate Smooth Muscle Cells (SMCs). These SMCs migrate from the tunica media into the intima, where they begin to proliferate rapidly.
The migrated SMCs synthesize extracellular matrix components, including collagen and elastin. This forms a tough fibrous cap over the growing lipid core, which now contains dead foam cells and extracellular cholesterol. This structure is known as an atheromatous plaque.
Inflammatory enzymes (matrix metalloproteinases) secreted by macrophages gradually degrade the collagen in the fibrous cap, thinning it out. If the cap ruptures, the highly thrombogenic necrotic core is exposed to the bloodstream. Platelets aggregate immediately, forming a clot that can completely occlude the artery — leading to myocardial infarction (heart attack) or ischemic stroke.
Markers like LDL-C, HDL-C, ApoB, Lp(a), hs-CRP, fasting glucose, and HbA1c all relate to the stages above. Upload your bloodwork to see your own values read in this context.
