Table 1. Effect of Batimastat on lumen diameter during remodeling in Bmal1-KO mice.
End diastolic lumen diameter was measured live in vivo through echo ultrasound imaging using M-Mode (see methods). Vascular remodelling evident as a lumen diameter reduction was evident by 1 week post-arterial ligation in wild-type mice, treated with vehicle control (LC remodeling, top table). Batimastat treatment in WT mice accelerated a constrictive response demonstrated as a significant reduction in lumen diameter, 1 day post-ligation. However, by 3 weeks after the ligation, constrictive remodeling in LC WT treated with Batimastat was attenuated, exhibiting increased lumen diameter compared to LC WT mice treated with vehicle (N= 4/ group, *p<0.05 by unpaired T-test). Bmal1-KO mice exhibited no inward remodeling, but exhibited outward remodeling which was significant at 2 weeks in the vehicle administrated group and in an analogous manner to WT, became accelerated, albeit outward, occurring with significance at 4 days and 2 weeks post-ligation in the Batimastat treated group (top table) (N= 4/ group, *p<0.05 by one-way ANOVA versus corresponding preligation lumen diameter). Batimastat and Bmal1 mutation did not affect lumen diameter in control, contralateral RC (bottom table).
| LC (mm) | Pre-ligation | 1 Day Post-ligation | 4 Days Post-ligation | 1 Week Post-ligation | 2 Weeks Post-ligation | 3 Weeks Post-ligation |
|---|---|---|---|---|---|---|
| WT Vehicle | 0.30 +/- 0.016 | 0.26+/- 0.022 | 0.26+/- 0.016 | 0.25+/- 0.005 * | 0.21+/- 0.007 * | 0.16+/- 0.012 * |
| WT Batimastat | 0.29+/- 0.015 | 0.23+/- 0.007 * | 0.17+/- 0.008 * | 0.2+/- 0.004 * | 0.17+/- 0.009 * | 0.2+/- 0.012 *† |
| KO Vehicle | 0.30+/- 0.015 | 0.29+/- 0.011 | 0.34+/- 0.009 | 0.36+/- 0.009 | 0.39+/- 0.029 # | 0.35+/- 0.042 |
| KO Batimastat | 0.29+/- 0.007 | 0.27+/- 0.012 | 0.38+/- 0.007 # | 0.37+/- 0.021 | 0.39+/- 0.007 # | 0.35+/- 0.017 |
| RC (mm) | Pre-ligation | 1 Day Post-ligation | 4 Days Post-ligation | 1 Week Post-ligation | 2 Weeks Post-ligation | 3 Weeks Post-ligation |
| WT Vehicle | 0.28+/- 0.012 | 0.28+/- 0.009 | 0.31+/- 0.01 | 0.31+/- 0.012 | 0.31+/- 0.011 | 0.29+/- 0.015 |
| WT Batimastat | 0.28+/- 0.019 | 0.27+/- 0.008 | 0.27+/- 0.005 | 0.27+/- 0.012 | 0.26+/- 0.003 | 0.27+/- 0.007 |
| KO Vehicle | 0.31+/- 0.016 | 0.32+/- 0.005 | 0.32+/- 0.005 | 0.33+/- 0.021 | 0.34+/- 0.036 | 0.33+/- 0.012 |
| KO Batimastat | 0.31+/- 0.016 | 0.32+/- 0.005 | 0.33+/- 0.016 | 0.33+/- 0.019 | 0.33+/- 0.037 | 0.31+/- 0.015 |