Coronary Artery Disease II: Pathophysiology

Vascular endothelium damage results from multiple etiological factors including hypertension, which creates mechanical stress on vessel walls; smoking, which introduces free radicals and toxins; diabetes mellitus, which causes hyperglycemia-induced oxidative stress; and dyslipidemia, characterized by elevated LDL cholesterol levels. These factors collectively compromise the protective barrier function of endothelial cells.

Monocytes are recruited to inflamed endothelial areas through adhesion molecules and migrate into the arterial intima, where they differentiate into macrophages. These macrophages engulf oxidized LDL and transform into foam cells, which accumulate to form fatty streaks—the earliest visible lesions in atherosclerosis and precursors to advanced plaques.

Stable plaques feature thick fibrous caps and small lipid cores, making them less prone to rupture. Unstable plaques have thin caps and large lipid cores, rendering them more susceptible to rupture. When unstable plaques rupture, the exposed lipid core triggers platelet activation and thrombus formation, potentially occluding the coronary artery.

Low-density lipoproteins penetrate damaged endothelial layers and accumulate in the subendothelial space, where they undergo oxidation and become highly immunogenic molecules. Oxidized LDL attracts immune cells and stimulates release of pro-inflammatory cytokines, amplifying vascular inflammation and perpetuating the atherosclerotic disease process.

Smooth muscle cells migrate from the medial layer to the intima under the influence of growth factors such as platelet-derived growth factor. Once in the intima, they secrete extracellular matrix proteins like collagen and elastin, creating a fibrous cap over the lipid core and forming the structural foundation of atherosclerotic plaques.

When a thrombus significantly narrows or completely blocks a coronary artery, it reduces blood flow to the heart muscle, causing myocardial ischemia and oxygen deprivation. Prolonged ischemia leads to myocardial necrosis, commonly known as a heart attack, which can result in serious cardiac dysfunction or death.

Damaged endothelial cells lose their ability to produce nitric oxide, a potent vasodilator and anti-inflammatory mediator, and cannot inhibit adhesion of inflammatory cells. This dysfunction fosters a pro-inflammatory and pro-thrombotic environment, setting the stage for acute coronary syndrome pathophysiology and subsequent atherosclerotic plaque development.