Introduction
Patients with diabetes mellitus that receive coronary stents experience greater stent restenosis and thrombosis, leading to adverse clinical outcomes. Impaired stent healing is linked to elevated endovascular inflammation, but
in vivo
data is lacking. Here, we assessed stent inflammation and tissue healing in diabetic rabbits, using intravascular molecular-structural near-infrared fluorescence (NIRF)-optical frequency domain imaging (OFDI).
Methods
A bare-metal stent (3.5x12mm) was implanted in the infrarenal aorta of alloxan-induced diabetic rabbits (n=5). At day 28, intravascular NIRF-OFDI was performed. Prosense VM110 (5mg/kg IV 24 hrs before imaging; ex/em 750/780 nm) enabled NIRF molecular imaging of inflammatory cathepsin activity. Structural OFDI stent endothelialization (coverage) was simultaneously assessed in 0.5mm intervals. Aortas were then harvested for
ex vivo
fluorescence reflectance imaging (FRI), electrochemical stent dissolution, and cathepsin B immunostaining.
Results
At day 28, stent NIRF inflammatory cathepsin protease activity was enhanced compared to the non-stented aorta (50.9±2.0 vs. 26.1±0.6 nM; p<0.0001). OFDI demonstrated greater average stent edge restenosis (proximal and distal 2mm stent edge neointimal area, 1.63±0.12 vs. mid 2 mm stent 0.50±0.05 mm
2
; p<0.0001), with less de-endothelialized struts at the stent edges (2.1±1.7% vs. 14.0±4.1% mid stent; p=0.03). Stent edge NIRF inflammation was also greater (60.8±3.4 vs. 40.8±1.4 nM mid stent; p=0.0005), and correlated with neointima formation (R=0.43; p=0.003). Conversely, NIRF inflammation negatively tracked with OFDI-uncovered stent struts (R=-0.42; p=0.004). FRI corroborated the enhanced stent-edge NIRF pattern. Matched histopathology revealed cathepsin B expression in NIRF-positive regions.
Conclusions
Intravascular NIRF-OFDI molecular-structural imaging demonstrates that NIRF inflammatory protease activity is linked to increased bare-metal stent edge neointimal formation, but inversely relates to uncovered stent struts. This translatable approach provides new insights into stent inflammation and healing, and may ultimately inform the risk of stent restenosis and thrombosis.
TCTAP C-160 0/300 Re-stenting for Treatment of Bare Metal Stent Restenosis in a Patient with Adult Coarctation of Aorta
