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

Xuening (Neal) Chen, Kalisha D. O'Neill, Xianming Chen, Kraiwiporn Kiattisunthorn, Vincent H. Gattone, Sharon Moe

Research output: Contribution to journalArticle

46 Citations (Scopus)

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
Pages (from-to)211-219
Number of pages9
JournalAmerican Journal of Nephrology
Volume34
Issue number3
DOIs
StatePublished - Sep 2011

Fingerprint

Vascular Calcification
Matrix Metalloproteinases
Chronic Renal Insufficiency
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Aorta
Matrix Metalloproteinase Inhibitors
Vascular Smooth Muscle
Smooth Muscle Myocytes
Extracellular Matrix
Tissue Inhibitor of Metalloproteinase-1
Serum
Phosphorus
Up-Regulation
Enzyme-Linked Immunosorbent Assay
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Activation of arterial matrix metalloproteinases leads to vascular calcification in chronic kidney disease. / Chen, Xuening (Neal); O'Neill, Kalisha D.; Chen, Xianming; Kiattisunthorn, Kraiwiporn; Gattone, Vincent H.; Moe, Sharon.

In: American Journal of Nephrology, Vol. 34, No. 3, 09.2011, p. 211-219.

Research output: Contribution to journalArticle

Chen, Xuening (Neal) ; O'Neill, Kalisha D. ; Chen, Xianming ; Kiattisunthorn, Kraiwiporn ; Gattone, Vincent H. ; Moe, Sharon. / Activation of arterial matrix metalloproteinases leads to vascular calcification in chronic kidney disease. In: American Journal of Nephrology. 2011 ; Vol. 34, No. 3. pp. 211-219.
@article{328b9682489d44c3a877bc7d552d75db,
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. 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.",
keywords = "Chronic kidney disease, Gelatinase, Matrix metalloproteinase, Vascular calcification",
author = "Chen, {Xuening (Neal)} and O'Neill, {Kalisha D.} and Xianming Chen and Kraiwiporn Kiattisunthorn and Gattone, {Vincent H.} and Sharon Moe",
year = "2011",
month = "9",
doi = "10.1159/000330175",
language = "English",
volume = "34",
pages = "211--219",
journal = "American Journal of Nephrology",
issn = "0250-8095",
publisher = "S. Karger AG",
number = "3",

}

TY - JOUR

T1 - Activation of arterial matrix metalloproteinases leads to vascular calcification in chronic kidney disease

AU - Chen, Xuening (Neal)

AU - O'Neill, Kalisha D.

AU - Chen, Xianming

AU - Kiattisunthorn, Kraiwiporn

AU - Gattone, Vincent H.

AU - Moe, Sharon

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

KW - Chronic kidney disease

KW - Gelatinase

KW - Matrix metalloproteinase

KW - Vascular calcification

UR - http://www.scopus.com/inward/record.url?scp=79960662431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960662431&partnerID=8YFLogxK

U2 - 10.1159/000330175

DO - 10.1159/000330175

M3 - Article

C2 - 21791917

AN - SCOPUS:79960662431

VL - 34

SP - 211

EP - 219

JO - American Journal of Nephrology

JF - American Journal of Nephrology

SN - 0250-8095

IS - 3

ER -