A 64-year-old man becomes unconscious after experiencing severe retrosternal chest pain. He has a history of hypertension and dyslipidemia but is nonadherent with his prescribed medication regimen. He also has a long history of heavy smoking. Paramedics are called, and the man is pronounced dead on arrival to the emergency department. An autopsy reveals diffuse atherosclerotic vascular disease involving the coronary arteries. One of the atheromatous plaques in the left main artery has a ruptured fibrous cap with an overlying occluding thrombus. Which of the following cellular components is most directly involved in formation of the fibrous portion of this patient's plaque?
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Atherosclerosis is a chronic inflammatory and fibroproliferative disease triggered by endothelial cell injury from chronic hemodynamic stress (eg, hypertension), hypercholesterolemia, diabetes mellitus, and/or cigarette smoking. The resulting endothelial cell dysfunction allows adherence and migration of monocytes and T lymphocytes into the intima (Choices B and D). Increased vascular permeability also allows LDL cholesterol into the intima, where it becomes oxidized and is phagocytosed by the accumulating macrophages to produce lipid-laden foam cells (Choice C).
Over time, the infiltrating leukocytes and dysfunctional endothelium (along with adherent activated platelets [Choice A]) release cytokines and growth factors (eg, platelet-derived growth factor, fibroblast growth factor, endothelin-1) that promote migration and proliferation of medial smooth muscle cells (SMCs) into the intima.
This chronic inflammatory state drives further deposition of oxidized LDL cholesterol and proliferation of SMCs with increased production of extracellular matrix proteins (eg, collagen, proteoglycans), eventually forming the fibrous cap typical of a mature atheroma (ie, fibrofatty plaque). As the atheroma grows larger, the likelihood increases that the fibrous cap will be disrupted (atherosclerotic plaque rupture), followed by rapid luminal thrombosis that has catastrophic clinical consequences (eg, acute coronary syndrome, sudden cardiac death).
Educational objective:
Medial smooth muscle cells are responsible for synthesizing the extracellular matrix proteins (eg, collagen, proteoglycans) that form the fibrous cap of a mature atheroma. Progressive atheroma enlargement increases the likelihood of plaque rupture with resulting luminal thrombosis.