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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1486.)
© 2003 American Heart Association, Inc.

Editorial

SR-BI

A New Player in an Old Game

Omar L. Francone

From Pfizer Global Research and Development, Groton, Conn.

Correspondence to Omar L. Francone, PhD, Pfizer Global Research and Development, Department of Cardiovascular and Metabolic Diseases, Eastern Point Rd, Groton, CT 06340. E-mail Omar_L_Francone@groton.pfizer.com

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Monocyte-derived macrophages are among the first cells to accumulate in atherosclerotic lesions. Primarily, they appear to scavenge lipids and lipoproteins from fatty streaks, but their long-term presence and accumulation of cholesterol and cholesteryl esters is the hallmark of atherosclerosis. Atherogenesis begins by a perturbation in the endothelium. Subsequently, blood monocytes and later T lymphocytes adhere to the endothelium and migrate into the intima. Macrophages accumulate cholesteryl esters and triglyceride in cytoplasmic droplets, leading to the formation of foam cells. Although questions still remain regarding the relative contribution of environmental and/or genetic factors to the cholesterol accumulation and initiation of the atherosclerotic process, it is believed that foam cell development and ultimately atherosclerosis result from a defective control in the intimal round-trip of cholesterol.

See pages 1589

Cholesterol accumulation in macrophages occurs independently of LDL receptors and results from the uptake of retained and modified apoB-containing lipoproteins by scavenger receptors,¹ which are not under a cholesterol-feedback regulation. The scavenger receptor superfamily is composed of many members with diverse structures, expression patterns, and functions.² Scavenger receptor class A types I and II, the class B scavenger receptors (CD36 and CD68), LOX-1, and possible others are implicated in the unrestrictive cholesteryl ester accumulation in macrophages, lipid droplet formation and ultimately, atherosclerosis.³ As intracellular cholesterol levels increase, endogenous cholesterol biosynthesis and LDL receptor expression are repressed through inhibition of the sterol regulatory element-binding protein (SREBP) pathway.⁴ This mechanism is insufficient to maintain cholesterol homeostasis in the face of continued cholesterol uptake by scavenger-receptor-dependent mechanisms. . . . [Full Text of this Article]

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