Premium
Perivascular endothelial cells increase positive remodeling by down regulation of matrix metalloproteinase (MMP)‐2 in porcine arteriovenous grafts
Author(s) -
Nugent Helen,
Sjin Robert Tjin Tham,
White Desmond,
Milton Luther,
Manson Roberto,
Lawson Jeffrey,
Edelman Elazer
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a231-d
Subject(s) - medicine , stenosis , lumen (anatomy) , anastomosis , external jugular vein , matrix metalloproteinase , fibrosis , arteriovenous anastomosis , jugular vein , vein , cardiology , anatomy , surgery
Vascular access dysfunction is a major problem in hemodialysis patients. Arteriovenous (AV) grafts have a patency rate of only 50% at 1 year. Vein maturation is an important factor in the success of an AV graft, the vein must remodel to accommodate arterial blood flow and pressure. We examined the role of perivascular endothelial implants in venous remodeling and stenosis. The data presented here provides insight into the mechanism of the implants and AV graft failure. End‐to‐side carotid artery‐jugular vein AV grafts were created in swine and the anastomoses wrapped with Gelfoam ® matrices containing porcine endothelial cells (PAE, n = 10) or control matrices without cells (n = 10). The biological response was investigated at 3 days and 1‐month post‐operatively. PAE implants significantly increased venous lumen gain. The treated veins increased in diameter from 1.04 ± 0.09 at day 0 to 2.9 ± 0.56 at 1‐month, P <0.05, while control veins remained unchanged from 1.28 ± 0.13 at day 0 to 1.29 ± 0.35 at 1‐month (Fig. 1). The implants also reduced the percent stenosis by 81%, P <0.05. These data correlated with a significant reduction in MMP‐2 expression (Fig. 2), adventitial fibrosis and neovascularization in treated veins compared to control, P <0.05. This study suggests that PAE implants significantly increased venous lumen diameter and reduced stenosis at 1‐month in porcine AV grafts. Funding provided by Pervasis Therapeutics. 12