Aberrant expression of FcγRIIIA (CD16) contributes to the development of atherosclerosis

Previous studies have documented that Fc receptor III A of immunoglobulin G (Fc gamma RIIIA, also named CD16) is involved in the development of coronary heart disease (CHD). However, the mechanism responsible for Fc gamma RIIIA's in contribution to CHD development remains largely unclear. Herein, we investigated the possible role of Fc gamma RIIIA in the development of atherosclerosis. Our results showed that the elevated level of Fc gamma RIIIA on monocytes closely correlated to the adhesive efficiency of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, we also observed increased population of CD16(+) monocytes and elevated CD16 level on monocytes in ApoE(-/-) mice with characterized atherosclerosis after feeding with high-fat diet for 10 weeks. The enhancement of CD16 on monocytes closely correlated to increased content of MMP-9 in aorta and increased inflammatory cytokines in sera. In addition, similar to simvastatin, recombinant human M-CSF represented a robust inhibitory influence on plaque instability and inflammation. Taken together, these data established that Fc gamma RIIIA (CD16)-mediated signaling orchestrated by interaction between monocytes and HUVECs, coupled with inflammatory cytokine stimulation and MMP activation, as a fundamental pathway linked to the development of atherosclerotic formation. Inhibition of Fc gamma RIIIA or its signaling thus might represent a promising approach for the prevention and treatment of CHD. (C) 2012 Elsevier B.V. All rights reserved.