title: Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque.
abstract: Unstable coronary syndromes, initiated by rupture of an atherosclerotic plaque, may involve the activation of matrix metalloproteinases (MMPs). The regulation of MMP activity is complex and involves three steps. First, an inactive pro-MMP is transcriptionally regulated, a process that is likely to involve the transcription factor activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB). Secondly, the pro-MMP is proteolytically cleaved into an active MMP. Plasmin has been suggested to be the major activator of MMPs in vivo. Thirdly, the activated MMP can be inhibited by tissue inhibitors of metalloproteinase (TIMPs). We investigated if expression of MMP9 and its potential regulators are induced in unstable coronary plaques. Atherosclerotic plaques from patients with stable (n=22) and unstable (n=39) angina were obtained by directional coronary atherectomy and analysed by semiquantitative RT-PCR and immunohisto-chemistry. Plasma was collected for ELISA analysis. mRNA for MMP9 as well as plasminogen activator inhibitor-1 (PAI-1) was increased in unstable plaques, while tissue type plasminogen activator (tPA) expression was similar in stable and unstable plaques. Plaques from unstable patients had an increased infiltration of macrophages and T-lymphocytes, nuclear localisation of AP-1 and the NF-kappaB subunit p65, as well as increased positive immunostaining for MMP9 and tPA. Plasma MMP9 antigen was elevated in unstable patients. MMP9 is expressed in the unstable coronary atherosclerotic plaque, as are its transcriptional and posttranscriptional regulators.
authors.affiliation: Crafoord Laboratory, South Hospital, Stockholm, Sweden.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.forename: Istvan
authors.initials: I
authors.lastname: Herzfeld
authors.forename: Magareta
authors.initials: M
authors.lastname: Klein
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Hansson
authors.forename: Guro
authors.initials: G
authors.lastname: Valen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9