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DOI: 10.1055/s-2007-987237
Aged Garlic Extract Inhibits CD36 Expression and Foam Cell Formation in Human Macrophages
Introduction: During formation of early atherosclerotic lesions, expression of CD36, a class B scavenger receptor on macrophages, is crucially involved in the uptake of oxidized low-density lipoprotein (oxLDL) and foam-cell formation. Aged garlic extract (AGE) has been shown to inhibit the progression of coronary calcifications in patients with coronary artery disease [1]. We hypothesized that AGE may inhibit the differentiation of human monocytes (THP-1 cells) into macrophages, the expression of CD36, and the cellular uptake of oxLDL [2]. Methods and Results: THP-1 cells were stimulated for 72h with phorbol 12-myristate 13-acetate (PMA, 10 nmol/L) in the absence or presence of AGE (5g/L) to differentiate them into macrophages. CD36 expression, as measured by flow cytometry, was significantly suppressed by 61.8±13.9% in AGE treated cells. Dexamethasone (10 nmol/L) was used as a negative, and troglitazone (500 nmol/L) as a positive control. THP-1 cells in the presence of PMA were incubated with or without AGE for 72h, followed by incubation with DiI-labeled OxLDL (50mg/L) for 3h, and the fluorescence intensity was measured by flow cytometry. AGE significantly inhibited DiI-oxLDL uptake into PMA-stimulated THP-1 cells by 85.6±2.8%. As expression of CD36 on macrophages is at least partly regulated by the peroxisome proliferator-activated receptor-γ (PPARγ) pathway, we performed electrophoretic mobility shift assays to identify the binding of nuclear proteins to a consensus oligonucleotide DNA sequence contained in PPARγ responsive elements (PPRE). AGE inhibited the binding of nuclear proteins to a consensus PPRE sequence compared to PMA-stimulated controls. Troglitazone and GW-9662 (20µmol/L) were used as the respective positive and negative controls. Conclusions: These data indicate that AGE inhibits CD36 expression and oxLDL uptake in macrophages via modulation of the PPARγ pathway. This suggests a mechanism by which the extract could reduce the formation and progression of atherosclerotic lesions, as shown in a recent clinical trial [1].
Acknowledgement: Supported by Wakunaga of America, Mission Viejo, CA., USA.
References: [1] Budoff, M. et al. (2004) Prev Med 39: 985–91. [2] Ide, N. et al. (2006) J Nutr 136: 755S-8S.