Evolution of shear stress, protein expression, and vessel area in an animal model of arterial dilatation in hemodialysis grafts.

PURPOSE

To evaluate the wall shear stress, protein expression of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2, and vessel area over time in a porcine model for polytetrafluoroethylene (PTFE) hemodialysis grafts.

MATERIALS AND METHODS

In 21 pigs, subtotal renal infarction was created, and 28 days later, a PTFE graft was placed to connect the carotid artery to the ipsilateral jugular vein. Phase-contrast magnetic resonance imaging was used to measure blood flow and vessel area at 1, 3, 7, and 14 days after graft placement. Wall shear stress was estimated from the law of Poiseuille. Animals were killed at day 3 (n = 7), day 7 (n = 7), and day 14 (n = 7) and expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined at the grafted and control arteries.

RESULTS

The mean wall shear stress of the grafted artery was higher than in the control artery at all time points (P < .05). It peaked by day 3 and decreased by days 7-14 as the vessel area nearly doubled. By days 7-14, there was a significant increase in active MMP-2 followed by a significant increase in pro-MMP-9 and active MMP-9 by day 14 (P < .05, grafted artery vs control). TIMP-1 expression peaked by day 7 and then decreased, whereas TIMP-2 expression was decreased at days 7-14.

CONCLUSIONS

The wall shear stress of the grafted artery peaks by day 3, with increased MMP-2 activity by days 7-14, followed by increase pro-MMP-9 and active MMP-9 by day 14. In addition, the vessel area nearly doubled.