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(American Journal of Pathology. 2001;159:1981-1986.)
© 2001 American Society for Investigative Pathology

Short Communication

Aluminum Chloride Pretreatment of Elastin Inhibits Elastolysis by Matrix Metalloproteinases and Leads to Inhibition of Elastin-Oriented Calcification

Michael Bailey^*, Hui Xiao^*, Matthew Ogle and Naren Vyavahare^*

From the Department of Bioengineering,^*
Clemson University, Clemson, South Carolina; and St. Jude Medical Inc.,
St. Paul, Minnesota

Calcification of elastin occurs in many pathological cardiovascular diseases including atherosclerosis. We have previously shown that purified elastin when subdermally implanted in rats undergoes severe calcification and aluminum chloride (AlCl₃) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl₃ pretreatment. Subdermal implantation of AlCl₃-pretreated elastin showed significantly lower MMP-9 and MMP-2 activity surrounding the implant as compared to the control implants. AlCl₃ pretreatment also significantly inhibited elastin implant calcification at the seven-day implant period (AlCl₃-pretreated 4.07 ± 1.27, control 23.82 ± 2.24 µg/mg; p<0.0001). Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl₃ inhibited elastolysis by MMP-9. We also demonstrate significant suppression of MMP-2 activity in aortic wall segments of AlCl₃-pretreated porcine bioprosthetic heart valve implants as compared to control valve implants in sheep mitral valve replacement studies. AlCl₃ pretreatment also significantly inhibited calcification of elastin in this model. Thus, we conclude that aluminum ion binding to elastin prevents MMP-mediated elastolysis and thus prevents elastin calcification.

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