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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:412.)
© 2002 American Heart Association, Inc.

Vascular Biology

Novel 5' Exon of Scavenger Receptor CD36 Is Expressed in Cultured Human Vascular Smooth Muscle Cells and Atherosclerotic Plaques

Jean-Marc Zingg^*; Roberta Ricciarelli^*; Enzo Andorno; Angelo Azzi

From the Institute of Biochemistry and Molecular Biology (J.-M.Z., A.A.), University of Bern, Bern, Switzerland, Dipartimento Trapianti (E.A.), Ospedale S. Martino, Genoa, and Dipartimento Medicina Sperimentale, Genova, Italy.

Correspondence to Prof A. Azzi, Institut für Biochemie und Molekularbiologie, Universität Bern, Bühlstrasse 28, CH-3012 Bern, Switzerland. E-mail angelo.azzi{at}mci.unibe.ch

CD36, a member of the scavenger receptor family, is centrally involved in the uptake of oxidized low density lipoproteins (oxLDLs) from the bloodstream. During the atherosclerotic process, the lipid cargo of oxLDL accumulates in macrophages and smooth muscle cells (SMCs), inducing their pathological conversion to foam cells. Increased expression of CD36 occurs in human atherosclerotic lesions, and CD36 knockout mice show reduced uptake of modified LDLs and reduced atherosclerosis. Here, we describe a novel exon 1b and extended CD36 promoter in human SMCs. Exon 1b is specifically transcribed in activated aortic SMCs and mainly expressed in atherosclerotic plaques. Thus, switching to exon 1b transcription may be an important step for the activation of SMCs and their conversion to foam cells. Using an antisense oligonucleotide to exon 1b, we inhibit CD36 translation and highly reduce oxLDL uptake. The antisense to exon 1b does not affect CD36 in cell lines not expressing the new exon. The possibility of a novel antiatherosclerotic therapy and the use of exon 1b as a marker of atherosclerosis are discussed.

Key Words: scavenger receptors • CD36 • atherosclerosis • oxidized LDL • gene structure

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