Elastin degradation and calcification in an abdominal aorta injury model

Role of matrix metalloproteinases

Dina M. Basalyga, Dan T. Simionescu, Wanfen Xiong, Bernard Timothy Baxter, Barry C. Starcher, Narendra R. Vyavahare

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

Background - Elastin calcification is a widespread feature of vascular pathology, and circumstantial evidence exists for a correlation between elastin degradation and calcification. We hypothesized that matrix metalloproteinase (MMP)-mediated vascular remodeling plays a significant role in elastin calcification. Methods and Results - In the present studies, we determined that short-term periadventitial treatment of the rat abdominal aorta with low concentrations of calcium chloride (CaCl2) induced chronic degeneration and calcification of vascular elastic fibers in the absence of aneurysm formation and inflammatory reactions. Furthermore, the rate of progression of calcification depended on the application method and concentration of CaCl2 applied periarterially. Initial calcium deposits, associated mainly with elastic fibers, were persistently accompanied by elastin degradation, disorganization of aortic extracellular matrix, and moderate levels of vascular cell apoptosis. Application of aluminum ions (known inhibitors of elastin degradation) before the CaCl2-mediated injury significantly reduced elastin calcification and abolished both extracellular matrix degradation and apoptosis. We also found that MMP-knockout mice were resistant to CaCl2-mediated aortic injury and did not develop elastin degeneration and calcification. Conclusion - Collectively, these data strongly indicate a correlation between MMP-mediated elastin degradation and vascular calcification.

Original languageEnglish (US)
Pages (from-to)3480-3487
Number of pages8
JournalCirculation
Volume110
Issue number22
DOIs
StatePublished - Nov 30 2004

Fingerprint

Abdominal Injuries
Elastin
Abdominal Aorta
Matrix Metalloproteinases
Vascular Calcification
Elastic Tissue
Extracellular Matrix
Blood Vessels
Apoptosis
Calcium Chloride
Wounds and Injuries
Aluminum
Knockout Mice
Aneurysm
Ions
Pathology
Calcium

Keywords

  • Apoptosis
  • Arteriosclerosis
  • Calcium
  • Collagen
  • Metalloproteinases

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Elastin degradation and calcification in an abdominal aorta injury model : Role of matrix metalloproteinases. / Basalyga, Dina M.; Simionescu, Dan T.; Xiong, Wanfen; Baxter, Bernard Timothy; Starcher, Barry C.; Vyavahare, Narendra R.

In: Circulation, Vol. 110, No. 22, 30.11.2004, p. 3480-3487.

Research output: Contribution to journalArticle

Basalyga, Dina M. ; Simionescu, Dan T. ; Xiong, Wanfen ; Baxter, Bernard Timothy ; Starcher, Barry C. ; Vyavahare, Narendra R. / Elastin degradation and calcification in an abdominal aorta injury model : Role of matrix metalloproteinases. In: Circulation. 2004 ; Vol. 110, No. 22. pp. 3480-3487.
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