Published Online
on November 15, 2004

A more recent version of this article appeared on November 30, 2004

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Submitted on May 5, 2004
Revised on July 20, 2004
Accepted on September 8, 2004

Elastin Degradation and Calcification in an Abdominal Aorta Injury Model. Role of Matrix Metalloproteinases

Dina M. Basalyga MS, Dan T. Simionescu PhD, Wanfen Xiong PhD, B. Timothy Baxter MD, Barry C. Starcher PhD, and Narendra R. Vyavahare PhD^*

From the Department of Bioengineering (D.M.B., D.T.S., N.R.V.), Clemson University, Clemson, SC; the Department of Surgery (W.X., B.T.B.), University of Nebraska Medical Center, Omaha, Neb; and the Department of Biochemistry (B.C.S.), University of Texas Health Center, Tyler, Tex.

^* To whom correspondence should be addressed. E-mail: narenv{at}clemson.edu.

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.

Key words: calcium • metalloproteinases • collagen • arteriosclerosis • apoptosis

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