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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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 lb 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.

Original languageEnglish (US)
Pages (from-to)412-417
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Atherosclerosis
  • CD36
  • Gene structure
  • Oxidized LDL
  • Scavenger receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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