Expression of macrophage (Mphi) scavenger receptor, CD36, in cultured human aortic smooth muscle cells in association with expression of peroxisome proliferator activated receptor-gamma, which regulates gain of Mphi-like phenotype in vitro, and its implication in atherogenesis.
CD36 is one of the major receptors for oxidized low density lipoproteins belonging to macrophage (Mphi) scavenger receptor (SR) class B and is thought to play an important role in the foam cell formation from monocyte-Mphi in the atherosclerotic lesions. Although it has been hypothesized that smooth muscle cells (SMCs) may be the other origin of foam cells in vivo, supporting data are still very limited. In the present study, we have tested the expression of a variety of SRs, including CD36, in 8 lots of primary human aortic SMCs (HASMCs) explanted from 8 different donors. Functional CD36 was expressed in cultured HASMCs, and the levels of expression were widely ranged between the lots. SR class A (SR-A) was expressed abundantly in CD36-negative lots. Other Mphi markers, such as CD32 and CD68, were expressed in all lots tested. These data suggest that the cultured HASMCs gained an Mphi-like phenotype. To determine the mechanism for the above-described phenotypic change, we have tested the expression of a nuclear receptor, peroxisome proliferator activated receptor-gamma, in those cells. This nuclear receptor was abundantly expressed in CD36-positive lots, whereas c-fms was expressed abundantly in CD36-negative/SR-A-positive lots. The synthetic ligand of peroxisome proliferator activated receptor-gamma, troglitazone, upregulated the expression of CD36 only in CD36-positive lots. These observations demonstrate that cultured HASMCs can gain an Mphi-like phenotype, possibly classified by the expression of CD36 or SR-A. The present study may support the possibilities of transformation of HASMCs into foam cells in vivo.
Matsumoto
K
K
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Hirano
K
K
Nozaki
S
S
Takamoto
A
A
Nishida
M
M
Nakagawa-Toyama
Y
Y
Janabi
M Y
MY
Ohya
T
T
Yamashita
S
S
Matsuzawa
Y
Y
D000328:Adult; D001011:Aorta; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D018955:CD36 Antigens / Q000032:analysis / Q000235:genetics*; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008264:Macrophages / Q000737:chemistry* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
D018955:CD36 Antigens; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors