Abstract: The angiotensin II receptor-1 blockers have generally been shown to have antiatherogenic effects, and dendritic cells (DCs) are the most efficient antigen presenting cells that play an active role in the development of atherosclerosis through inflammatory-immune responses. Here, we tested the hypothesis that the antiatherogenic effect of losartan, the first angiotensin II receptor-1 blockers, might partly be mediated by attenuating DCs maturation. In this study, we showed that oxidized low-density lipoprotein (oxLDL) and angiotensin II (Ang II) could induce the maturation of human monocyte-derived DCs, stimulate CD83, HLA-DR expressions and IL-12, interferon-gamma secretions and increase the capacity of DCs to stimulate T-cell proliferation, which were suppressed by losartan. OxLDL could promote the autocrine secretion of Ang II by DCs and upregulate the expressions of 3 scavenger receptors SR-A, CD36, and LOX-1. Losartan reduced oxLDL-induced LOX-1 expression but not SR-A and CD36 expressions. Ang II could only upregulate the LOX-1 expression, which was reduced by losartan. OxLDL- and Ang II-induced upregulation of CD83 and secretion of IL-12 were all attenuated by LOX-1 neutralizing antibody. In conclusion, losartan could attenuate the oxLDL- and Ang II-induced immune maturation of human monocyte–derived DCs partly through downregulation of the LOX-1 expression.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Reprints: Junbo Ge, MD, Department of Medicine/Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China (e-mail: firstname.lastname@example.org).
Supported by National Basic Research Program of China (2011CB503905), Shanghai Natural Science Foundation (12ZR1405200) from the Shanghai Science and Technology Committee.
D. Huang and H. Lu contributed equally to this work.
The authors report no funding or conflicts of interest.
Received February 2, 2012
Accepted April 4, 2012