Received 29 January 2009; received in revised form 24 March 2009; accepted 27 March 2009.
Purpose
The first aim of the present study was to create a mouse carotid artery–to–jugular vein arteriovenous (AV) fistula model. This model was used to test the hypothesis that there is increased gene expression of matrix metalloproteinase (MMP)–2 and MMP-9 at the venous stenosis.
Materials and Methods
Ten male FVB/NJ mice underwent the creation of an AV fistula between the left carotid artery and ipsilateral jugular vein, with the contralateral vessels serving as controls. Two mice died 1 day after surgery and the other eight were euthanized at day 28. Reverse transcriptase polymerase chain reaction was performed in five mice, with the grafted vein and control vein tissue used to determine the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2. Immunohistochemical analysis of the grafted vein and control vein was performed in three mice.
Results
Venous stenosis formed at the outflow vein, characterized by a thickened neointima with cells staining positive for α–smooth muscle actin. There was increased expression of MMP-2, tissue inhibitor of metalloproteinase (TIMP)–1, and TIMP-2 by day 28 at the venous stenosis compared with control vein.
Conclusions
A mouse carotid artery–to–jugular vein AV fistula model was developed and used to demonstrate increased expression of several markers known to be associated with AV fistula stenosis. The model may be useful in investigating mechanisms responsible for AV fistula venous stenoses.
ABSTRACT