Induced expression of lectin-like oxidized ldl receptor-1 in vascular smooth muscle cells followingChlamydia pneumoniaeinfection and its down-regulation by fluvastatin

Abstract

Microorganisms such as Chlamydia pneumoniae have been shown to infect vascular cells and are believed to contribute to vascular inflammation and atherosclerotic plaque development. Plasma levels of oxidized low density lipoprotein (oxLDL) have received considerable attention as potential predictors of prognosis in atherosclerotic diseases. Lectin-like oxidized LDL receptor-1 (LOX-1) is one of the major receptors for oxidized LDL. It was investigated whether C. pneumoniae infection can stimulate expression of LOX-1 in vascular smooth muscle cells. Expression of LOX-1 in VSMC was measured by RT-PCR and immunoblotting following C. pneumoniae infection. To examine the pharmacological effect of a HMG-CoA reductase inhibitor on LOX-1 expression, cells were co-incubated with fluvastatin immediately after infection. A dose and time dependent expression of LOX-1mRNA and protein was found in C. pneumoniae infected SMC. After heat and UV light treatment of the chlamydial inoculum the level of LOX-1 was reduced to that of mock-infected cultures. Furthermore, treatment of infected cells with fluvastatin decreased LOX-1 expression to baseline levels. The up-regulation of LOX-1 induced by C. pneumoniae could lead to continued lipid accumulation in atherosclerotic lesions. Together with the widespread expression of LOX-1, this might contribute to the epidemiologic link between C. pneumoniae infection and atherosclerosis. The effect of lowering the LOX-1 expression by fluvastatin may provide a pharmacological option of limiting oxLDL uptake via its scavenger receptor.

Chlamydophila pneumoniae infection and cardiovascular disease

“…C. pneumoniae also has a role in lipid accumulation in the vessel wall by upregulating lecithin-like oxidized LDL receptors (LOX-1) in both endothelial and vascular smooth muscle cells. [4344] In the same period, four studies[45–48] did not find convincing evidence of presence of Chlamydophila genome in the atheromatous tissue, and argued in favor of alternative mechanisms. However, it is likely that C. pneumoniae infection may only be providing an initial trigger and is transient rather than persistent.…”

Cytosolic lipid inclusions formed during infection by viral and bacterial pathogens

“…These results suggest that C. pneumoniae induces macrophage foam cell formation by the native LDL receptor in the presence of LDL [31]. In 2010 Prochnau et al presented experimental evidence that C. pneumoniae induces also the expression of the scavenger receptor LOX-1 (oxidized LDL receptor-1) in vascular smooth muscle cells [64]. Lin et al showed that GroEL1, a heat shock protein 60 of C. pneumoniae, induces LOX-1 expression in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits [65].…”

LOX‐1: Its cytotopographical variance and disease stress

“…Such infection induces expression of LOX‐1 in VSMCs. Treatment with fluvastatin, an HMG‐CoA‐reductase inhibitor, decreases LOX‐1 expression . The upregulation of LOX‐1 by such infections and a reduction by fluvastatin provides clue of lipid accumulation in atherosclerotic lesions in microbial infections.…”