Novel 5' exon of scavenger receptor CD36 is expressed in cultured human vascular smooth muscle cells and atherosclerotic plaques.
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.
Zingg
Jean-Marc
JM
Institute of Biochemistry and Molecular Biology, University of Bern, Bern, Switzerland.
Ricciarelli
Roberta
R
Andorno
Enzo
E
Azzi
Angelo
A
D024506:5' Flanking Region; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005091:Exons; D017930:Genes, Reporter; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D018955:CD36 Antigens; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B