Activation of arterial matrix metalloproteinases leads to vascular calcification in chronic kidney disease

Neal X. Chen, Kalisha D. O'Neill, Xianming Chen, Kraiwiporn Kiattisunthorn, Vincent H. Gattone, Sharon M. Moe

Research output: Contribution to journalArticle

49 Scopus citations

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)211-219
Number of pages9
JournalAmerican journal of nephrology
Volume34
Issue number3
DOIs
StatePublished - Sep 2011

Keywords

  • Chronic kidney disease
  • Gelatinase
  • Matrix metalloproteinase
  • Vascular calcification

ASJC Scopus subject areas

  • Nephrology

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