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Chapter 48: Cardiovascular Disease: The Metabolic Syndrome and Atherosclerosis

You are examining the characteristics of monocyte transmigration through a monolayer of endothelial cells in a culture system. Your studies reveal that the addition of an experimental compound induces a significant increase in the rate of monocyte transmigration. This compound most likely induced the expression of which in the monolayer of endothelial cells?

A. E-selectin

B. endothelial-leukocyte adhesion molecule-1, ELAM-1

C. Intercellular adhesion molecule-1, ICAM-1

D. monocyte chemotactic protein-1, MCP-1

E. vascular cell adhesion molecule-1, VCAM-1

Answer D: Monocyte chemotactic protein-1, MCP-1 (also known as chemokine C-C motif ligand 2, CCL2) is expressed by endothelial cells in response to inflammatory activation, injury, or infection. MCP-1 is the major monocyte chemoattractant inducing migration of monocytes to the site of endothelial cell activation. Once recruited to these sites the monocytes invade the underlying intimal layer where they differentiate into macrophages. Once in the intima these macrophages phagocytose oxLDL and other lipids and cellular debris becoming foam cells which further activates their proinflammatory state. The secretion of factors such as TNF-α and IL-1β by foam cells induces smooth muscle cell proliferation and their migration into the intima.

During a routine examination of a 58-year-old male patient, blood work indicates a significant elevation in the level of homocysteine. Elevated levels of homocysteine in the blood have been shown to correlate with cardiovascular dysfunction and thus, it is imperative to determine the cause of this patient's homocysteine levels. Analysis for activity of which of the following enzymes is likely to show a defect resulting in the elevation in serum homocysteine in this patient?

A. cystathionine β-synthase

B. dihydrofolate reductase

C. dihydropteridine reductase

D. methionine adenosyltransferase

E. methionine synthase

Answer A: Homocystinurias/homocystinemias represent a family of inherited disorders resulting from defects in several of the genes involved in the conversion of methionine to cysteine. The most common causes of homocystinuria are defects in the cystathionine β-synthase (CBS) gene. Common symptoms of homocystinuria are dislocated optic lenses, osteoporosis, lengthening and thinning of the long bones, and an increased risk of abnormal blood clotting (thromboembolism). Some instances of genetic homocystinuria respond favorably to pyridoxine therapy, suggesting that in these cases the defect in CBS is a decreased affinity for the cofactor, pyridoxal phosphate.

You are examining a 63-year-old woman who has come to you complaining of headache, light-headedness, and facial ...

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