Losartan inhibits cellular uptake of oxidized LDL by monocyte-macrophages from hypercholesterolemic patients

Angiotensin II (Ang II) and oxidized LDL (Ox-LDL) are risk factors for athe rosclerosis, and both of them contribute to macrophage cholesterol accumula tion, the hallmark of early atherosclerosis. As Ang II was shown to increas e macrophage uptake of Ox-LDL, we investigated the effect of losartan, an A ng II receptor antagonist with antiatherogenic properties, on the cellular uptake of Ox-LDL by human monocyte-derived macrophages (HMDM) from hypercho lesterolemic patients. Eight normotensive hypercholesterolemic patients wer e treated with losartan (50 mg/day) for a period of 4 weeks. Losartan thera py did not significantly affect the degradation of native LDL by the patien ts' HMDM. However, losartan therapy significantly reduced HMDM uptake of Ox -LDL as shown by a 78% reduction in Ox LDL cell-association and a 21% reduc tion in Ox-LDL degradation. CD36 (an Ox-LDL receptor) mRNA expression in HM DM obtained after losartan treatment was decreased by 54% compared to HMDM obtained before treatment. The ability of losartan to inhibit HMDBI CD36 mR NA expression and, hence, Ox-LDL uptake and macrophage foam cell formation is probably related to the blockage of Ang II binding to the cell surface a nd thus to the prevention of Ang II atherogenic effects. (C) 2000 Academic Press.