Document Detail

Matrix metalloproteinase inhibition reduces intimal hyperplasia in a porcine arteriovenous-graft model.
MedLine Citation:
PMID:  14743149     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The patency of arteriovenous (AV) polytetrafluoroethylene grafts for hemodialysis is impaired by intimal hyperplasia (IH) at the venous outflow tract. IH mainly consists of vascular smooth muscle cells, fibroblasts, and extracellular matrix proteins. Because matrix metalloproteinases (MMPs) are enzymes able to degrade extracellular matrix proteins such as elastin and collagen and also stimulate migration of vascular smooth muscle cells, we hypothesized that BB2983 (a broad-spectrum MMP inhibitor) could reduce IH in AV grafts.
METHODS: In 12 pigs, AV grafts were created bilaterally between the carotid artery and the jugular vein. Six pigs received the oral MMP inhibitor (MMPi), and six pigs served as a control. Four weeks after AV shunting, the grafts and adjacent vessels were excised and underwent histologic analysis. Quantification of elastin content was performed on Elastin von Gieson-stained sections.
RESULTS: At the venous outflow tract, IH was strongly inhibited after MMPi when compared with the control group (1.02 +/- 0.26 mm(2) vs 2.14 +/- 0.38 mm(2); P =.027). The medial area did not differ significantly. In the control group elastin density decreased compared with nonoperated veins. This decrease was not observed in the MMPi group (nonoperated, 6.3% +/- 0.4%; MMPi, 7.2% +/- 0.7% vs untreated, 3.6% +/- 0.5%; P =.0004). Outward remodeling of the vein was not influenced by MMP inhibition.
CONCLUSION: MMPi reduces IH formation at the venous outflow tract of AV grafts in pigs, probably by inhibiting elastin degradation. These data suggest that MMP inhibitors might be useful for minimizing IH in AV grafts, thus prolonging patency rates of AV grafts in patients on hemodialysis.
Joris I Rotmans; Evelyn Velema; Hence J M Verhagen; Jan D Blankensteijn; Dominique P V de Kleijn; Erik S G Stroes; Gerard Pasterkamp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  39     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-02-19     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  432-9     Citation Subset:  IM    
Department of Experimental Cardiology, University Medical Center, Utrecht, The Netherlands.
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MeSH Terms
Arteriovenous Shunt, Surgical
Blood Vessel Prosthesis*
Carotid Arteries / surgery
Elastin / metabolism
Graft Occlusion, Vascular / prevention & control*
Jugular Veins / surgery
Matrix Metalloproteinases / antagonists & inhibitors*
Renal Dialysis
Tunica Intima / pathology*
Vascular Patency
Reg. No./Substance:
9002-84-0/Polytetrafluoroethylene; 9007-58-3/Elastin; EC 3.4.24.-/Matrix Metalloproteinases

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