title: Activation of arterial matrix metalloproteinases leads to vascular calcification in chronic kidney disease.
abstract: BACKGROUND
  The objective of the current study was to determine if altered regulation of matrix metalloproteinases (MMPs) may predispose to extracellular matrix degradation, facilitating arterial calcification in chronic kidney disease (CKD) using a progressive model of CKD-MBD, the Cy/+ rat.
  
  
  METHODS
  Sera were collected from normal or CKD rats at various times and MMP-2 and MMP-9 levels determined by ELISA or zymography. Aorta tissue was harvested at sacrifice for RT-PCR and immunostaining. Calcification of aorta rings was assessed with MMP inhibitors.
  
  
  RESULTS
  There was an increase in MMP-2, MMP-9, TIMP-1, and RUNX-2 expression in the aorta with progressive CKD, and increased MMP-2 activity in the serum. Immunostaining revealed increased expression of MMP-2 and MMP-9 in areas of aorta calcification. There was also an upregulation of MMP-2 and MMP-9 in vascular smooth muscle cells (VSMC) from CKD rats. MMP inhibitors decreased calcification of aorta rings from normal and CKD rats. High phosphorus increased MMP-2 and MMP-9 expressions in VSMC from normal rats but not from CKD rats.
  
  
  CONCLUSIONS
  MMP-2 and MMP-9 expression and activity are increased with progressive CKD, and blockade of MMP activity can inhibit arterial calcification. These data suggest degradation of the extracellular matrix is a critical step in the pathogenesis of arterial calcification in CKD.
authors.affiliation: Division of Nephrology, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.forename: Kalisha D
authors.initials: KD
authors.lastname: O'Neill
authors.forename: Xianming
authors.initials: X
authors.lastname: Chen
authors.forename: Kraiwiporn
authors.initials: K
authors.lastname: Kiattisunthorn
authors.forename: Vincent H
authors.initials: VH
authors.lastname: Gattone
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
mesh_terms: D000818:Animals; D002908:Chronic Disease; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications*; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000502:physiology*; D051381:Rats; D015854:Up-Regulation; D061205:Vascular Calcification / Q000209:etiology*
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9