title: Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae: the potential role of Chlamydia pneumoniae infection in the progression of atherosclerosis.
abstract: Chlamydia pneumoniae infection implicated as an important etiologic factor of atherosclerosis, especially in coronary artery disease (CAD), was found in vitro to be associated with the induction of matrix metalloproteinases (MMPs). An extracellular matrix metalloproteinase inducer (EMMPRIN)/ membrane-type 1 matrix metalloproteinase (MT1-MMP) system which induces and activates MMPs, is suggested to be functional and were upregulated in the failing myocardium. However, the upstream regulation of MMPs by C. pneumoniae within atheroma itself remains unclear. We evaluated the seroepidemiologic study of C. pneumoniae infection in CAD patients (n= 391) and controls (n=97) and performed histopathological and in vitro analysis in atherosclerotic vascular tissues obtained from patients with seropositive to C. pneumoniae (n=20), by using immunochemistry for C. pneumoniae, EMMPRIN/MT1-MMP, MMP-2, and MMP-9. The seropositive rates of both anti-C. pneumoniae IgG and IgA were 56.7% in CAD group and 43.3% in control group (P=0.033). Seropositive rate was increased in subgroups of CAD patients without conventional coronary risk factors compared to those with conventional risk factors. Immunoreactivities of EMMPRIN, MT1-MMP, MMP-2, and MMP-9 were increased in the atheromatous plaque itself, predominantly in immunoreactive macrophages/mononuclear cells to C. pneumoniae. Furthermore, Western blot analysis showed that EMMPRIN and MMP-2 were detected more prominently in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. Zymographic analysis revealed that activities of MMP-2 and MMP-9 were more increased in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. The present study demonstrated upstream regulation of MMPs can be induced by C. pneumoniae within atheromatous plaque itself. These findings help to understand the potential role of C. pneumoniae in the progression of atherosclerosis.
authors.affiliation: Yonsei Cardiovascular Center, Cardiovascular Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eui Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Kim
authors.forename: Bum Kee
authors.initials: BK
authors.lastname: Hong
authors.forename: Hyuck Moon
authors.initials: HM
authors.lastname: Kwon
authors.forename: Young Goo
authors.initials: YG
authors.lastname: Song
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Byun
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Whang
authors.forename: Hyun-Seung
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001161:Arteriosclerosis / Q000150:complications / Q000201:enzymology / Q000382:microbiology* / Q000473:pathology*; D051926:Basigin; D015153:Blotting, Western; D002690:Chlamydia Infections / Q000150:complications* / Q000201:enzymology / Q000453:epidemiology / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D018450:Disease Progression; D005109:Extracellular Matrix / Q000201:enzymology; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; D008562:Membrane Glycoproteins; D051926:Basigin; D018093:Gelatinases; D020782:Matrix Metalloproteinases