Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model.

Materials and methods: Three 4-week-old male ApoE-deficient (ApoE(-/-))-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n=10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 μg/mouse) was administered and assessed by optical imaging 24h after injury and compared to another group (n=3) which was injected two days after injury and sacrificed another day later.

Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 ± 18.9 vs. 10.4 ± 1.0; P=0.028). Injection of unlabeled GPVI-Fc 20 h and 3h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 ± 4.6, while intact carotids showed a signal of 9.2 ± 1.1; P=0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 ± 6.18 vs. 16.48 ± 5.15; P=0.039). Three days after injury and 24h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 ± 2.76 vs. 14.76 ± 1.59; P=0.519).

Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.