Aged garlic extract inhibits homocysteine-induced scavenger receptor CD36 expression and oxidized low-density lipoprotein cholesterol uptake in human macrophages in vitro

Aim of the study: 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. Results: Incubation with Hcy (200 p.,M 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 PPAR gamma response element. Preincubation with AGE significantly inhibited Dil-labeled OxLDL uptake. Conclusions: These data indicate that AGE inhibits CD36 expression and OxLDL uptake in human macrophages by modulating the PPAR gamma pathway, and suggest that the extract could be useful for the prevention of atherosclerotic lesions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.