A 60-year-old man comes to the office with a 6-month history of exertional chest pain that remits with rest. His other medical conditions include hypertension, diabetes mellitus, and hypercholesterolemia. An exercise stress test is positive for inducible ischemia. Cardiac catheterization shows 80% occlusion of the right coronary artery and 60% occlusion of the left coronary artery. The first step in the pathogenesis of this patient's coronary artery disease most likely involved which of the following cell types?

Question

A 60-year-old man comes to the office with a 6-month history of exertional chest pain that remits with rest.  His other medical conditions include hypertension, diabetes mellitus, and hypercholesterolemia.  An exercise stress test is positive for inducible ischemia.  Cardiac catheterization shows 80% occlusion of the right coronary artery and 60% occlusion of the left coronary artery.  The first step in the pathogenesis of this patient's coronary artery disease most likely involved which of the following cell types?

Quizplus · Accepted Answer

11ec160b_38bf_1168_9249_8772ae287496_MD0001_00 This patient's presentation is consistent with coronary artery atherosclerosis. The pathogenesis of atherosclerosis likely begins with endothelial cell injury. Chronic endothelial cell injury may result from hypertension (and related hemodynamic factors), hyperlipidemia, smoking, and diabetes mellitus. Such injury leads to endothelial cell dysfunction and/or exposure of subendothelial collagen (endothelial cell denudation). Endothelial cell dysfunction results in monocyte and lymphocyte adhesion and migration into the intima (Choice C), while exposure of subendothelial collagen promotes platelet adhesion (Choice F). Growth factors produced by monocytes and platelets stimulate medial smooth muscle cell (SMC) migration into the intima (Choice G). At the same time, increased vascular permeability allows LDL cholesterol into the intima, where it is phagocytosed by the accumulating macrophages and SMCs to produce lipid-laden foam cells (fatty streak). The continued release of cytokines and growth factors results in a chronic inflammatory state within the underlying intima. This promotes further deposition of LDL cholesterol within the intima and stimulates SMC proliferation with increased production of collagen and proteoglycans. Necrosis of foam cells results in release of toxic oxidized LDL into the extracellular matrix, perpetuating a cycle of injury. The lesion eventually organizes into a core of lipid debris surrounded by monocytes and lymphocytes covered by a fibrous cap with intermixed SMCs (fibrofatty atheroma). (Choice B) Fibroblasts do not contribute significantly to atheroma formation. The fibrous tissue, including the fibrous cap, of atheromas is synthesized by SMCs that have migrated to the intimal layer in which the plaque forms. (Choice D) Mast cells are not significantly involved in the pathogenesis of atherosclerosis. (Choice E) Pericytes are pluripotent cells that surround the smallest blood vessels (especially postcapillary venules). Because atherosclerosis affects the large elastic arteries and large- and medium-sized muscular arteries, these cells do not play a significant role. Educational objective: Atherosclerosis is initiated by repetitive endothelial cell injury, which leads to a chronic inflammatory state in the underlying intima of large elastic arteries as well as in large- and medium-sized muscular arteries.

A 60-Year-Old Man Comes to the Office with a 6-Month