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Alpha-tocopherol decreases CD36 expression in human monocyte-derived macrophages
1Division of Clinical Biochemistry and Human Metabolism, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Insights
Alpha-tocopherol (AT) reduces scavenger receptor expression and cholesterol buildup in macrophages. This finding supports AT's role in preventing atherosclerosis.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Nutritional Science
Background:
- Cholesterol-laden macrophages are central to atherosclerosis development.
- The scavenger receptor CD36 binds oxidized low-density lipoprotein (OxLDL) and is upregulated in atherosclerotic lesions.
Purpose of the Study:
- To investigate the impact of alpha-tocopherol (AT) on CD36 expression and cholesteryl ester accumulation in human macrophages.
- To assess the antiatherogenic potential of AT.
Main Methods:
- Human monocytes were cultured into macrophages and enriched with varying doses of AT.
- Macrophages were incubated with oxidized LDL (OxLDL) or acetylated LDL (AcLDL).
- CD36 expression was measured by flow cytometry; scavenger receptor class A (SR-A) activity and cholesteryl ester accumulation were quantified.
Main Results:
- AT (≥50 μM) significantly reduced OxLDL- and AcLDL-induced CD36 expression.
- AT treatment decreased DiI-AcLDL and DiI-OxLDL uptake.
- Cholesteryl ester accumulation was significantly inhibited by AT (77% for AcLDL, 42% for OxLDL).
Conclusions:
- Alpha-tocopherol decreases both CD36 and SR-A expression in human macrophages.
- AT significantly reduces cholesteryl ester accumulation, indicating a potential role in preventing atherosclerosis.
Abstract:
Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B scavenger receptor, CD36, binds oxidized low density lipoprotein (OxLDL), is found in atherosclerotic lesions, and is upregulated by OxLDL. We tested the effects of alpha-tocopherol (AT) enrichment of human monocyte-derived macrophages on CD36 expression and cholesteryl ester accumulation. Monocytes isolated from normal volunteers were cultured into macrophages. Macrophages were enriched overnight with various doses of AT (25, 50, and 100 microM). LDL from normal volunteers was oxidized or acetylated (AcLDL) and incubated with macrophages for 48 h at a concentration of 50 or 100 microg/ml. CD36 expression was assessed by flow cytometry. Quantitative analysis of scavenger receptor class A (SR-A) activity was performed with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide perchlorate (DiI)-labeled LDL. CD36 expression was maximal after 8;-10 days of culture. AT (> or =50 microM) significantly decreased CD36 expression upregulated by OxLDL and AcLDL (P < 0.01). Other antioxidants (beta- or gamma-tocopherol) or protein kinase C inhibitors failed to decrease CD36 expression. Concomitantly, DiI-AcLDL and DiI-OxLDL uptake was significantly decreased after AT treatment (P < 0.001). Cholesteryl ester accumulation was significantly decreased after AT enrichment (AcLDL + AT, 77% inhibition; OxLDL + AT, 42% inhibition). In conclusion, AT decreases both CD36 and SR-A expression and cholesteryl ester accumulation in human macrophages. This provides additional scientific support for the antiatherogenic properties of AT.