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(Circulation. 2004;110:3480-3487.)
© 2004 American Heart Association, Inc.

Molecular Cardiology

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; 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.

Correspondence to Naren Vyavahare, 501 Rhodes Hall, Department of Bioengineering, Clemson University, Clemson, SC 29634. E-mail narenv{at}clemson.edu

Received May 5, 2004; revision received July 20, 2004; accepted September 8, 2004.

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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