This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mason, R. P. Articles by Jacob, R. F. Search for Related Content PubMed PubMed Citation Articles by Mason, R. P. Articles by Jacob, R. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Related Collections Pathophysiology Cell biology/structural biology

(Circulation. 2003;107:2270.)
© 2003 American Heart Association, Inc.

Special Review

Membrane Microdomains and Vascular Biology

Emerging Role in Atherogenesis

R. Preston Mason, PhD; Robert F. Jacob, PhD

From the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston (R.P.M.), and Elucida Research, Beverly (R.P.M., R.F.J.), Mass.

Correspondence to R. Preston Mason, PhD, 100 Cummings Center, Suite 135L, Beverly, MA 01915. E-mail rpmason@elucidaresearch.com

Key Words: atherosclerosis • cholesterol • lipids • pharmacology • vasculature

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

	Introduction

 
The classic model of cell plasma membrane organization is that of a uniform, fluid environment in which protein and lipid constituents diffuse rapidly in an unrestricted fashion. Recent experimental evidence, however, reveals a far more complex membrane organization consisting of microdomains assembled from lipid constituents that have distinct biophysical characteristics. Such microdomains or "lipid rafts" are typically detergent-resistant and highly enriched with cholesterol and sphingolipids compared with the overall membrane lipid bilayer environment.¹ These defined regions of lipid domains sequester proteins that mediate signal transduction in a variety of cell types, including endothelial cells and myocytes. Lipid rafts move or "float" as a coherent structural unit within the liquid-disordered lipid bilayer and can also cluster with other rafts to form larger platforms. The basis for differences in fluidity between rafts and the surrounding membrane is the degree of hydrocarbon chain saturation; domains are characterized by sphingolipids containing saturated fatty acids that attract unesterified cholesterol. The planar sterol nucleus of cholesterol further restricts the mobility and rotation of sphingolipid acyl chains, resulting in limited random diffusion and an expanded molecular width as compared with the rest of the membrane.

The plasma membrane caveola is a lipid raft subtype that is the subject of intensive investigation. Caveolae typically appear as microscopic, flask-shaped invaginations along the membrane surface and are commonly found in endothelial cells, adipocytes, and smooth muscle cells (Figure). The principal protein component of caveolae is caveolin, a scaffolding protein that binds cholesterol efficiently and interacts with various signaling . . . [Full Text of this Article]

This article has been cited by other articles:

				R. F. Jacob and R. P. Mason Lipid Peroxidation Induces Cholesterol Domain Formation in Model Membranes J. Biol. Chem., November 25, 2005; 280(47): 39380 - 39387. [Abstract] [Full Text] [PDF]

				R. P. Mason, M. F. Walter, and R. F. Jacob Effects of HMG-CoA Reductase Inhibitors on Endothelial Function: Role of Microdomains and Oxidative Stress Circulation, June 1, 2004; 109(21_suppl_1): II-34 - II-41. [Abstract] [Full Text] [PDF]

				J. Lie, R. de Crom, T. van Gent, R. van Haperen, L. Scheek, F. Sadeghi-Niaraki, and A. van Tol Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins J. Lipid Res., May 1, 2004; 45(5): 805 - 811. [Abstract] [Full Text] [PDF]