title: C-reactive protein induces expression of matrix metalloproteinase-9: a possible link between inflammation and plaque rupture.
abstract: BACKGROUND
  Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute coronary syndromes (ACS). However, little is known about the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP) not only is an independent risk factor for cardiovascular events, but also may exert direct pro-atherosclerotic effects. Therefore, we aimed at determining whether CRP might induce MMP-9 in two different experimental conditions: 1) smooth muscle cells (SMCs) in vitro, and 2) patients with ACS.
  
  
  RESULTS
  Effects of increasing concentrations of CRP on MMP-9 expression were evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9 expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9 secretion. In contrast, no differences were found for TIMP-1 protein expression. In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries (controls, n=21), stable angina (n=24), and ACS (n=30). Both MMP-9 and CRP plasma levels were significantly increased across the coronary circulation only in patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP plasma levels was found.
  
  
  CONCLUSIONS
  CRP induced MMP-9 expression and activity in human SMCs in culture; patients presenting with ACS have increased transcoronary plasma levels of MMP-9 and CRP with a significant correlation between these two markers. This may explain the heightened risk of coronary events in subjects with elevated levels of CRP.
authors.affiliation: Department of Cardiothoracic and Respiratory Sciences, Division of Cardiology, Second University of Naples, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cimmino
authors.forename: Massimo
authors.initials: M
authors.lastname: Ragni
authors.forename: Plinio
authors.initials: P
authors.lastname: Cirillo
authors.forename: Gianluca
authors.initials: G
authors.lastname: Petrillo
authors.forename: Francesco
authors.initials: F
authors.lastname: Loffredo
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiariello
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Emanuela
authors.initials: E
authors.lastname: Falcinelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Golino
mesh_terms: D054058:Acute Coronary Syndrome / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D002097:C-Reactive Protein; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9