Atherosclerosis Topic Review

Atherosclerosis is the pathologic process by which cholesterol and calcium plaque accumulate within the arterial wall. The term “athero” means porridge and “sclerosis” means scarring, which is how atherosclerosis was first described on autopsy.

Atherosclerotic plaque within the coronary arteries is responsible for coronary artery disease and acute coronary syndromes and ST segment elevation MI, or STEMI. When present in the cerebrovascular system, stroke can occur. Atherosclerosis also contributes to peripheral arterial disease, aortic aneurysms, renal artery disease and mesenteric ischemia.

The pathophysiologic process by which atherosclerosis occurs is complex and somewhat controversial. The working theory includes four steps:

  1. Endothelial cell injury. This is likely the initial factor that begins the process of atherosclerotic plaque formation. Because the endothelium is constantly exposed to the circulation, any toxin present can result in damage, as occurs during tobacco use, diabetes and dyslipidemia. The continuous physical force exerted upon the endothelium also commonly plays a role, as the greatest atherosclerotic plaque occurs at arterial bifurcations ― i.e. the bifurcation of the left main coronary artery and the left anterior descending. Hypertension increases the physical force present.
  2. Lipoprotein deposition. When the endothelium is injured or disrupted, lipoprotein molecules can gain entry where they are then modified by oxidation (via free radicals or oxidizing enzymes) or glycation (in diabetes). This modified lipoprotein, or LDL, is inflammatory and able to be ingested by macrophages, creating “foam cells” and causing a “fatty streak” in the arterial wall.
  3. Inflammatory reaction. The modified LDL is antigenic and attracts inflammatory cells into the arterial wall. Also, after endothelial injury, inflammatory mediators are released further, increasing leukocyte recruitment.
  4. Smooth muscle cell cap formation. Smooth muscle cells migrate to the surface of the plaque, creating a “fibrous cap.” When this cap is thick, the plaque is stable; however, thin capped atherosclerotic plaques are thought to be more prone to rupture or erosion, causing thrombosis.