Expression of macrophage scavenger receptors in various human tissues and atherosclerotic lesions

Abstract

Expression of CD36 scavenger receptors on macrophages is involved in oxidized low-density lipoprotein (OxLDL) uptake and foam cell formation during atherosclerotic lesion development. It has been shown previously in vitro and in vivo that the atherosclerotic risk factor homocysteine (Hcy) stimulates macrophage CD36 expression and OxLDL uptake. We now examined the effects of aged garlic extract (AGE), a garlic preparation enriched in water-soluble organic sulfur-containing compounds, on Hcy-induced CD36 expression and foam cell formation in human monocytes/macrophages.Incubation with Hcy (200 μM for 72 h) in THP-1-derived macrophages and primary human macrophages caused a 37.8 ± 5.2% and 60.7 ± 4.2% increase in CD36 expression compared to control, respectively. Coincubation with AGE (5 mg/ml) significantly suppressed CD36 expression in THP-1 derived macrophages by 48.6 ± 9.0% compared to Hcy-incubated cells only. AGE (1–5 mg/ml) dose dependently inhibited Hcy-induced CD36 expression in primary human macrophages, and decreased binding of nuclear proteins to a PPARγ response element. Preincubation with AGE significantly inhibited DiI-labeled OxLDL uptake.These data indicate that AGE inhibits CD36 expression and OxLDL uptake in human macrophages by modulating the PPARγ pathway, and suggest that the extract could be useful for the prevention of atherosclerotic lesions.