Open AccessChlamydia pneumoniae induces expression of pro‐atherogenic factors through activation of the lectin‐like oxidized LDL receptor‐1
Author(s) -
Campbell Lee A.,
Lee Amy W.,
Rosenfeld Michael E.,
Kuo Chochou
Publication year - 2013
Publication title -
pathogens and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.983
H-Index - 105
ISSN - 2049-632X
DOI - 10.1111/2049-632x.12058
Subject(s) - downregulation and upregulation , chlamydophila pneumoniae , scavenger receptor , biology , chlamydia , microbiology and biotechnology , receptor , pathogenesis , glycan , antibody , immunology , lipoprotein , glycoprotein , chlamydiaceae , biochemistry , gene , cholesterol
Several lines of evidence have associated Chlamydia pneumoniae with cardiovascular disease including acceleration of atherosclerotic lesion progression in hyperlipidemic animal models by infection. Many of the pro‐atherogenic effects of oxidized low‐density lipoprotein (ox‐LDL) occur through the activation of the lectin‐like ox‐LDL receptor‐1 (LOX‐1). Chlamydia pneumoniae upregulates the expression of the LOX‐1 mRNA , promotes the uptake of ox‐LDL, and utilizes the LOX‐1 receptor for infectivity. The overall goal of this study was to determine whether C. pneumoniae organisms upregulated LOX‐1 protein expression in vascular cells and whether upregulation of pro‐atherogenic factors by C. pneumoniae occurred through LOX‐1. Chlamydia pneumoniae induced LOX‐1 protein expression in both endothelial cells and RAW macrophages. Upregulation was prevented by preincubation of cells with LOX‐1 antibody prior to infection. Similarly, C. pneumoniae upregulated protein expression of adhesion molecules, MMP‐1, and MMP‐3, which was mitigated by anti‐LOX‐1 antibody. Prior treatment of organisms with PNGase, which removes the chlamydial glycan that is N‐linked to the major outer membrane, abolished C. pneumoniae upregulation of LOX‐1. These studies suggest that activation of LOX‐1 expression occurs through binding of the chlamydial glycan and provides one mechanism by which C. pneumoniae infection could play a role in the pathogenesis of atherosclerosis.