Objectives: We investigated the mechanism by which C-reactive protein (CRP) affects pro-inflammatory activities of vascular smooth muscle cells (VSMCs). Methods and results: RT-PCR, flow cytometry, and immunoblotting assays consistently showed the expression of FcγRIIa by cultured VSMCs isolated from human coronary arteries. Immunofluorescence staining of human coronary artery plaque showed the co-localization of FcγRIIa with α-actin(+) VSMCs in atheromatous regions. Confocal microscopic image analysis of H2DCFDA-labeled cells showed that CRP induced intracellular reactive oxygen species (ROS) generation by FcγRIIa(+) HEK293T cells. Moreover, CRP time- and dose-dependently generated ROS in VSMCs through FcγRIIa activation. VSMCs mainly express NADPH oxidase 4 isoform (Nox4), the suppression of which using a specific siRNA completely abolished CRP-induced ROS generation by VSMCs. The downregulation of p22phox, a component of the active Nox4 complex, by transfecting with specific decoy oligomers and functional blocking of FcγRIIa not only inhibited the CRP-induced ROS generation but also reduced the degree of AP-1 and NF-κB activation, the production of MCP-1, IL-6, and ET-1, and the apoptotic changes of VSMCs in response to CRP. Conclusions: CRP-induced ROS generation by VSMCs, which requires functional activation of FcγRIIa and NADPH oxidase 4, orchestrates pro-inflammatory activities of VSMCs and may eventually promote atherogenesis and plaque rupture. © 2007 European Society of Cardiology.
Ryu, J., Lee, C. W., Shin, J. A., Park, C. S., Kim, J. J., Park, S. J., & Han, K. H. (2007). FcγRIIa mediates C-reactive protein-induced inflammatory responses of human vascular smooth muscle cells by activating NADPH oxidase 4. Cardiovascular Research, 75(3), 555–565. https://doi.org/10.1016/j.cardiores.2007.04.027