Strong epidemiological and pathological evidence supports a role for
Chlamydia pneumoniaeinfection in atherosclerosis and human coronary heart disease. Animal models have shown that C. pneumoniaedisseminates hematogenously in infected monocytes and macrophages, while in vitro data suggest that infected macrophages can transmit C. pneumoniaeinfection directly to endothelial cells. Endothelial cells may be key in vivo targets for C. pneumoniaeinfection; given that these cells are important in regulating the dynamics of the vessel wall, we used cDNA microarrays to study the transcriptional response of endothelial cells to infection with C. pneumoniae. cDNA arrays were used to characterize the mRNA expression profiles for 268 human genes following infection with C. pneumoniae, which were compared to mRNA profiles of uninfected cells. Selected genes of interest were further investigated by reverse transcription-PCR throughout a 24-h period of infection. C. pneumoniaeinfection upregulated mRNA expression for approximately 20 (8%) of the genes studied. Genes coding for cytokines (interleukin-1), chemokines (monocyte chemotactic protein 1 and interleukin-8), and cellular growth factors (heparin-binding epidermal-like growth factor, basic fibroblast growth factor, and platelet-derived growth factor B chain) were the most prominently upregulated. In addition to these families of genes, increases in mRNA levels for intracellular kinases and cell surface receptors with signal transduction activities were observed. Time course experiments showed that mRNA levels were upregulated within 2 h following infection. These results expand our knowledge of the response of endothelial cells to C. pneumoniaeby further defining the repertoire of C. pneumoniae-inducible genes and provide new insight into potential mechanisms of atherogenesis. In addition, the use of cDNA microarrays may prove useful for the study of host cell responses to C. pneumoniaeinfection during latent and replicative stages of infection and related pathology.