CD36, a Novel Receptor for Oxidized Low-Density Lipoproteins, Is Highly Expressed on Lipid-Laden Macrophages in Human Atherosclerotic Aorta

Abstract

Abstract-CD36 has been reported to be a receptor for oxidized LDL (Ox-LDL). In our previous study, the uptake of Ox-LDL in CD36-deficient macrophages was reduced by approximately 50% compared with that in control macrophages, suggesting an important role of CD36 as a receptor for Ox-LDL in humans. In the current study, we examined the immunohistochemical localization of CD36 in human aorta in comparison with that of scavenger receptor class A type I and type II (SRA). Cryostat sections were made from aortic tissues. For immunohistochemical staining, the following antibodies were used: (1) FA6-152, anti-CD36 antibody, and (2) SRI-2, which recognizes both type I and type II SRAs. Immunohistochemical staining for CD36 and SRA was performed using labeled streptavidin method. In macrophages scattered in aortic walls without atherosclerotic lesions, the expression of CD36 was hardly observed, whereas that of SRA was detected weakly but consistently. In contrast, in atherosclerotic lesions, macrophages around the core region showed a weak immunoreactivity to CD36 and a strong immunoreactivity to SRA. Furthermore, lipid-laden macrophages, which mainly existed in the core region, had a strongly positive immunoreactivity to CD36, but a low or moderate level of immunoreactivity to SRA. The distributions of CD36 and SRA were different from each other, and especially foamed, large-sized macrophages in atherosclerotic plaques tended to more abundantly express CD36 protein. These data demonstrate, for the first time, that the expression of both CD36 and SRA might be differentially regulated in aortic walls, and might play different roles in the formation of foam cells in atherosclerotic lesions.

Adipocyte-Derived Plasma Protein, Adiponectin, Suppresses Lipid Accumulation and Class A Scavenger Receptor Expression in Human Monocyte-Derived Macrophages

“…After lipid extraction, the cellular protein was dissolved in sodium hydroxide, and the protein concentration was determined by the method of Lowry et al 24 For detecting lipids accumulated in macrophages, oil red O staining was performed as previously described. 25 For detection of adiponectin on macrophages, anti-adiponectin monoclonal antibodies (ANOC 9108) were used as previously reported. 12 …”

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

“…Due to differential accessibility of lysines on the BSA molecule and the increased blocking of free amines by maleyl groups, fluorescent labeling required increasing stoichiometric ratios of FITC to mal-BSA with higher degree of maleylation. Therefore FITC:protein ratios of 2:1, 5:1, 10:1, 20:1 and 30:1 were employed for BSA maleylated at 0%, [8][9][10][11][12][13][14][15][16][17][18][19][20].5%, 29-69%, 82%, and 89%, respectively. Briefly, FITC (10mg/ml in DMSO) was added to mal-BSA in small aliquots over the course of 1 hour at room temperature while stirred.…”

“…(12,13) SR-A is expressed on the endothelial lining of the liver, adrenal sinusoids and on the high endothelial cells of the postcapillary venules in the lymph nodes; but, immunohistochemical staining analysis could not detect SR-A expression in the aortic endothelium of cows, mice and humans. (13) SR-A are strongly localized in the cap and interiorly in lesions at all stages (14,15). This makes the receptors an attractive target for a diagnostic or therapeutic agent.…”

Identification of a Novel Family of Oxidized Phospholipids That Serve as Ligands for the Macrophage Scavenger Receptor CD36

“…Its deficiency in humans has been correlated with alterations in myocardial fatty acid uptake, hypertrophic cardiac myopathy, and insulin resistance (6 -8). Recent studies (3, 4, 9 -11) have focused attention on CD36 as a participant in the atherosclerotic process because of its ability to recognize oxidized forms of LDL (oxLDL).1 CD36 mediates lipid accumulation and macrophage foam cell formation in vitro and in vivo (3,12,13). It is heavily expressed in lipid-rich * This work was supported in part by National Institutes of Health Grants HL62526, HL70621, HL61878 (to S. L. H.), GM21249 (to R. G. S.), and HL53315 (to H. F. H. and R. G. S.), and a Scientist Development grant from the American Heart Association (to E. A. P.).…”

“…1 CD36 mediates lipid accumulation and macrophage foam cell formation in vitro and in vivo (3,12,13). It is heavily expressed in lipid-rich * This work was supported in part by National Institutes of Health Grants HL62526, HL70621, HL61878 (to S. L. H.), GM21249 (to R. G. S.), and HL53315 (to H. F. H. and R. G. S.), and a Scientist Development grant from the American Heart Association (to E. A. P.).…”