FcγRIIa mediates C-reactive protein-induced inflammatory responses of human vascular smooth muscle cells by activating NADPH oxidase 4

53Citations
Citations of this article
12Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free