Remodeling of experimental arteriovenous fistula with increased matrix metalloproteinase expression in rats.
OBJECTIVE
Venous dilatation and wall thickening are part of the maturation of an arteriovenous fistula (AVF). However, the underlying mechanism of AVF remodeling remains unknown. We therefore studied whether matrix remodeling elicited by matrix metalloproteinases (MMPs) may contribute to AVF maturation.


METHODS
A femoral AVF model in rats was established by invagination of the distal end of the left femoral artery into the femoral vein after venotomy (fistula group). In the sham group, the left femoral artery was cut, but venous invagination was not performed. Changes in the hemodynamics and the diameter of the iliac vein were studied on days 3, 14, and 28, then the iliac vein was removed and examined for changes in wall thickness and expression of MMP-2 and MMP-9, type 4 tissue inhibitor of metalloproteinases (TIMP-4), and collagen I and III by immunohistochemical staining or Western blotting.


RESULTS
Femoral AVF resulted in a sixfold increase in blood flow in the fistula iliac vein and a gradual, but significant, increase in the thickness of the intima and media and marked up-regulation of MMP-2 and MMP-9, down-regulation of TIMP-4, as well as degradation of collagens I and III. The collagen I/III ratio was significantly higher in the 14-day fistula group (1.44 +/- 0.32) than in the sham group (0.82 +/- 0.15) and was even higher in the 28-day fistula group (1.76 +/- 0.21).


CONCLUSIONS
The present results confirmed our hypothesis that a high blood flow rate in the fistula vein affects the expression of MMPs and TIMP-4, resulting in the remodeling or maturation of the AVF. Remodeling is associated with degradation of collagen, with an increase in the collagen I/III ratio.
Chan
Chih-Yang
CY
Department of Surgery, Cardiovascular Division, Far Eastern Memorial Hospital, Panchaio, Taiwan.
Chen
Yih-Sharng
YS
Ma
Ming-Chieh
MC
Chen
Chau-Fong
CF
Chen
Chou-Fong
CF
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001783:Blood Flow Velocity; D001794:Blood Pressure; D015153:Blotting, Western; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D005263:Femoral Artery / Q000601:surgery*; D005268:Femoral Vein / Q000601:surgery*; D024022:Fibrillar Collagens / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006965:Hyperplasia; D007084:Iliac Vein / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D015854:Up-Regulation; D014664:Vasodilation; D000097792:Tissue Inhibitor of Metalloproteinase-4
D024042:Collagen Type I; D024061:Collagen Type III; D017364:Collagenases; D024022:Fibrillar Collagens; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4