Chlamydia pneumoniae infection of endothelial cells induces transcriptional activation of platelet-derived growth factor-B: a potential link to intimal thickening in a rabbit model of atherosclerosis.
Smooth muscle cell (SMC) proliferation and intimal thickening are hallmark features of atherosclerotic disease, and Chlamydia pneumoniae may contribute to atherogenesis by imparting biological effects on SMCs. An in vitro endothelial cell model and a normocholesterolemic rabbit model were used to test the hypothesis that infection with C. pneumoniae induces SMC growth factor production, SMC proliferation, and aortic intimal thickening. Using reverse-transcriptase polymerase chain reaction, it was demonstrated that C. pneumoniae infection of endothelial cells induced platelet-derived growth factor (PDGF)-B messenger RNA expression. In C. pneumoniae-infected rabbits, maximum intimal thickness (MIT) was significantly greater than that in uninfected animals (P< .0001). MIT correlated with the presence of C. pneumoniae antigen (P= .043) and PDGF-B (P= .002) in aortic tissues, and C. pneumoniae antigen was independently correlated with the presence of PDGF-B in aortic tissues (P= .009). These results suggest that C. pneumoniae-induced SMC proliferation and intimal thickening may be mediated through PDGF-B and may be a molecular mechanism by which C. pneumoniae infection could contribute to atherogenesis.
Coombes
Brian K
BK
Department of Medical Sciences, Father Sean O'Sullivan Research Centre, McMaster University, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
Chiu
Brian
B
Fong
Ignatius W
IW
Mahony
James B
JB
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D001161:Arteriosclerosis / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D023521:Chlamydophila Infections / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000382:microbiology / Q000473:pathology; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D017539:Tunica Intima / Q000473:pathology
D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger