Aluminum chloride pretreatment of elastin inhibits elastolysis by matrix metalloproteinases and leads to inhibition of elastin-oriented calcification.
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 (AlCl(3)) pretreatment of elastin inhibits calcification. In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl(3) pretreatment. Subdermal implantation of AlCl(3)-pretreated elastin showed significantly lower MMP-9 and MMP-2 activity surrounding the implant as compared to the control implants. AlCl(3) pretreatment also significantly inhibited elastin implant calcification at the seven-day implant period (AlCl(3)-pretreated 4.07 +/- 1.27, control 23.82 +/- 2.24 microg/mg; p<0.0001). Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl(3) inhibited elastolysis by MMP-9. We also demonstrate significant suppression of MMP-2 activity in aortic wall segments of AlCl(3)-pretreated porcine bioprosthetic heart valve implants as compared to control valve implants in sheep mitral valve replacement studies. AlCl(3) 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.
Bailey
M
M
Department of Bioengineering, Clemson University, Clemson, South Carolina 29634, USA.
Xiao
H
H
Ogle
M
M
Vyavahare
N
N
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002114:Calcinosis / Q000378:metabolism / Q000517:prevention & control*; D002712:Chlorides / Q000494:pharmacology*; D003240:Connective Tissue Diseases / Q000378:metabolism / Q000517:prevention & control*; D004547:Elastic Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004549:Elastin / Q000187:drug effects* / Q000378:metabolism; D006350:Heart Valve Prosthesis; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008943:Mitral Valve / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013552:Swine
D017607:Aluminum Compounds; D002712:Chlorides; D061965:Matrix Metalloproteinase Inhibitors; D000077410:Aluminum Chloride; D004549:Elastin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9