A 42-year-old man is found dead at home. His medical problems included hypertension and dyslipidemia, but he had been noncompliant with his medications. The patient had a lengthy smoking history and, despite constant urging from his physicians to stop smoking, he had only quit recently. An autopsy is requested by the family. Pathological examination shows complete thrombotic occlusion of the left main coronary artery and diffuse atherosclerotic vascular disease characterized by multiple atheromas. Along with a lipid core, these atheromas have a fibrous cap formed from dense deposition of collagen. Which of the following cells are directly responsible for synthesizing this fibrous cap?

Question

A 42-year-old man is found dead at home.  His medical problems included hypertension and dyslipidemia, but he had been noncompliant with his medications.  The patient had a lengthy smoking history and, despite constant urging from his physicians to stop smoking, he had only quit recently.  An autopsy is requested by the family.  Pathological examination shows complete thrombotic occlusion of the left main coronary artery and diffuse atherosclerotic vascular disease characterized by multiple atheromas.  Along with a lipid core, these atheromas have a fibrous cap formed from dense deposition of collagen.  Which of the following cells are directly responsible for synthesizing this fibrous cap?

Quizplus · Accepted Answer

11ec160b_38c8_875a_9249_755188f1518e_MD0001_00 Atherosclerosis is a chronic inflammatory and fibroproliferative disease. Endothelial cells, vascular smooth muscle cells (VSMCs), and leukocytes play an important role in the development and progression of this disease. The process is initiated by chronic hemodynamic stress and hyperlipidemia, which cause endothelial cell injury. This leads to increased expression of surface vascular cell-adhesion molecules (VCAMs) that allow adherence and migration of monocytes and T lymphocytes into the intima. The infiltrating leukocytes and dysfunctional endothelium release cytokines and growth factors (eg, platelet-derived growth factor, fibroblast growth factor, endothelin-1, interleukin-1) that promote migration and proliferation of VSMCs within the intima. VSMCs are also stimulated to synthesize extracellular matrix proteins (eg, collagen, elastin, proteoglycans) that form the fibrous cap typical of mature atheromas. Disruption of the fibrous cap with luminal thrombosis (atherosclerotic plaque rupture) has catastrophic clinical consequences and is responsible for the majority of acute coronary syndrome cases and sudden cardiac deaths. (Choice A) Endothelial cell dysfunction is the earliest pathophysiologic change that precedes the formation of atherosclerotic lesions. Endothelial injury results in increased lipid permeability, leukocyte (monocytes, T cells) and platelet recruitment, and migration and proliferation of VSMC from media to the intima. However, the VSMCs are directly responsible for the synthesis of new collagen. (Choice B) Fibroblasts are found infrequently in the tunica intima of blood vessels and are not significantly involved in atherosclerosis pathogenesis. (Choices C and E) Activated macrophages and T lymphocytes secrete growth factors that recruit the VSMCs responsible for forming the fibrous cap, but they are not directly responsible for the dense deposition of fibrillar collagen. Macrophages also produce matrix metalloproteinases and tissue factors that degrade the extracellular matrix, causing the formation of a large, soft lipid-rich core with thinning of the fibrous cap. Such vulnerable plaques have an increased propensity for rupture. Educational objective: Vascular smooth muscle cells (VSMCs) are the only cells within the atherosclerotic plaque capable of synthesizing structurally important collagen isoforms and other matrix components. Progressive enlargement of the plaque results in remodeling of the extracellular matrix and VSMC death, promoting development of vulnerable plaques with an increased propensity for rupture. __________ References: The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. (http://www.ncbi.nlm.nih.gov/pubmed/17933075) Pathogenesis of atherosclerosis. (http://www.ncbi.nlm.nih.gov/pubmed/16631513)

A 42-Year-Old Man Is Found Dead at Home