Adventitial remodeling with increased matrix metalloproteinase-2 activity in a porcine arteriovenous polytetrafluoroethylene grafts.
BACKGROUND
We hypothesized the source of early proliferating cells contributing to venous stenosis formation in a porcine hemodialysis grafts is the adventitia and media, and migration of these cells is greatest within the first two weeks following graft placement, resulting in increased matrix metalloproteinase-2 (MMP-2) activity.


METHODS
Polytetrafluoroethylene grafts from the iliac artery to the ipsilateral iliac vein were placed in 23 pigs and 5-Bromo-2'-deoxyuridine (BrdU) was given at 24 and 48 hours after surgery to assess cell proliferation and migration. Angiography and magnetic resonance angiography was performed. Animals were euthanized on day three (N= 6), day seven, (N= 5), day 14 (N= 6), and days 19 to 26 (N= 6) after graft placement, and stenotic tissue and unaffected contralateral iliac vein were removed for zymography and immunostaining.


RESULTS
Migration of cells derived from the adventitia and media peaked at day 14. Adventitial diameter of the stenotic vein decreased, while the intima to media ratio increased. MMP-2 activity peaks at day seven in the adventitia and days 19 to 26 in the intima.


CONCLUSIONS
These results confirm our hypothesis that the source of cells resulting in venous stenosis formation is derived from the adventitia and media, with cell migration being greatest within the first two weeks after graft placement with translocation of these cells into the intima at four weeks. MMP-2 activity peaks at day seven in the adventitia and again at days 19 to 26 in the intima. A key to limiting venous stenosis formation may lie in inhibiting MMP-2 by adventitial and medial targeting.
Misra
Sanjay
S
Department of Radiology, Division of Vascular Surgery, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. misra.sanjay@mayo.edu
Doherty
Michael G
MG
Woodrum
David
D
Homburger
Jay
J
Mandrekar
Jaywant N
JN
Elkouri
Stephane
S
Sabater
Enrique A
EA
Bjarnason
Haraldur
H
Fu
Alex A
AA
Glockner
James F
JF
Greene
Eddie L
EL
Mukhopadhyay
Debabrata
D
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D002465:Cell Movement; D006083:Graft Occlusion, Vascular / Q000209:etiology* / Q000473:pathology*; D006965:Hyperplasia; D007083:Iliac Artery / Q000201:enzymology / Q000473:pathology; D007084:Iliac Vein / Q000201:enzymology / Q000473:pathology; D018810:Magnetic Resonance Angiography; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D011138:Polytetrafluoroethylene; D013552:Swine; D013927:Thrombosis / Q000209:etiology / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D011138:Polytetrafluoroethylene; D020778:Matrix Metalloproteinase 2