Near-Infrared Fluorescence Imaging of Matrix Metalloproteinase 2 Activity as a Biomarker of Vascular Remodeling in Hemodialysis Access.

ABSTRACT

PURPOSE: To establish the capability of near-infrared fluorescence (NIRF) imaging for the detection of matrix metalloproteinase 2 (MMP-2) activity as a biomarker of vascular remodeling (VR) in arteriovenous fistulae (AVFs) in vivo. MATERIALS AND METHODS: AVFs were created in the right groins of Wistar rats (n = 10), and sham procedures were performed in the contralateral groins. Fistulography via a left common carotid artery approach confirmed stenosis (> 50%) in a subset of animals (n = 5) 4 weeks after AVF creation. After administration of MMP-2-activated NIRF probe, near-infrared imaging was performed in vivo and ex vivo of both the AVF and the sham-treated vessels to measure radiant efficiency of MMP-2-activated NIRF signal over background. Histologic analyses of AVF and sham-treated vessels were performed to measure VR defined as inward growth of the vessel caused by intimal thickening. RESULTS: AVFs demonstrated a significantly higher percentage increase in radiant efficiency over background compared with sham vessels (45.5 ± 56% vs 16.1 ± 17.8%; P = .008). VR in AVFs was associated with increased thickness of neointima staining positively for MMP-2 (161.8 ± 45.5 µm vs 73.2 ± 36.7 µm; P = .01). A significant correlation was observed between MMP-2 activity as measured by relative increase in radiant efficiency for AVFs and thickness of neointima staining positively for MMP-2 (P = .039). CONCLUSIONS: NIRF imaging can detect increased MMP activity in remodeled AVFs compared with contralateral sham vessels. MMP-2-activated NIRF signal correlates with the severity of intimal thickening. These findings suggest NIRF imaging of MMP-2 may be used as a biomarker of the vascular remodeling underlying stenosis.