Abstract-CD36 is one of the major receptors for oxidized low density lipoproteins belonging to macrophage (M) scavenger receptor (SR) class B and is thought to play an important role in the foam cell formation from monocyte-M 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 M markers, such as CD32 and CD68, were expressed in all lots tested. These data suggest that the cultured HASMCs gained an M-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-␥, 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. 3 and we have reported the molecular basis of this disorder by identifying 3 mutations in patients with CD36 deficiency. 4 -6 Using M from the patients, we have clarified that 1 of its major physiological functions is to act as a receptor for OxLDL, demonstrating that CD36 is responsible for Ϸ50% of the uptake of OxLDL. 7 Recently, several laboratories, including ours, have reported that the in vitro expression of CD36 in human M is regulated by the addition of OxLDL and some cytokines. 8 -10 Moreover, a ligand for peroxisome proliferator activated receptor-␥ (PPAR␥) upregulates the expression of CD36, subsequently causing the intracellular accumulation of lipids in human M. 9,10 These observations suggest that CD36 may be important for the formation of foam cells in vivo.Smooth muscle cells (SMCs) are 1 of the major components in atherosclerotic lesions. Previous studies have indicated that the change in SMCs from a differentiated contractile type to a dedifferentiated synthetic type is the critical phenotypic response for atherogenesis. 11,12 After the phenotypic change, SMCs migrate into the intima and proliferate, which leads to the narrowing of the arterial lumen physically and the production of cytokines and proteinases, causing chemical modification of the lesions and the development of atherosclerosis. 13
Methods
MaterialsHuman type-AB serum was purchased from ICN Biomedicals, Inc. Primary HASMCs and the growth media were purchased from Clonetics and Cascade. Information concerning the 8 donors who provided the serum (5 males and 3 females) are shown in the Table. The data were very limited because of privacy issues. The age of the donors ranged from 2.5 months to 29 years. All HASMCs were explanted from normal aortas without atherosclerosis. For immunohistochemical analysis, the...