Atherosclerosis has been linked to Chlamydia pneumoniae infection. In atherosclerotic arteries chlamydiae infect macrophages, endothelial cells, and smooth muscle cells (SMC). It has been suggested that the proteolysis of the extracellular matrix by matrix metalloproteinases (MMPs) is involved in the destabilisation and rupture of atherosclerotic plaques. In this study we investigated the expression of several MMPs and tissue inhibitors of MMP (TIMPs) in C. pneumoniae-infected SMC using reverse transcription-polymerase chain reaction analysis. Chlamydial infection of SMC up-regulated the mRNA levels of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) but did not affect the expression of MMP-2 and -9 (gelatinases). Additionally, the levels of TIMP-1 and -2 mRNA remained unchanged upon infection. Cells infected with C. pneumoniae secreted increased quantities of MMP-1 and -3 proteins as demonstrated by enzyme-linked immunosorbent assays. The ability of C. pneumoniae to stimulate the production of MMP-1 and -3 by SMC may be important for its pathogenic role in the progression of atherosclerotic disease.

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.

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