ABSTRACT
Objective: To investigate the impact of cathepsins S (CatS) on aortic ring-derived micro vascular cavity formation in experimental mice. Methods: Hindlimb ischemia model was established in CatS+/+ and CatS-/- mice, n=8 in each group. The blood flow in hindlimb was measured before ischemic surgery; immediately and 1, 4, 7, 14, 21 days after surgery. CatS+/+mice were further divided into 4 subgroups: Normal control subgroup, Selective CatS inhibitor (LHVS) subgroup, Non-selective CatS inhibitor (E64d) subgroup and MMP inhibitor (GM6001) subgroup; n=2 in each subgroup. The mice aortic ring-derived micro vascular cavity formation was observed by FITC-CD31 immunofluorescence method. Results: ① CatS-/- mice had inhibited blood flow recovery after ischemic surgery. Laser Doppler blood flow (LDBF) examination indicated that compared with CatS+/+group, CatS-/- group had slower hindlimb blood flow recovery, P<0.05;② CatS-/-group had the less aortic ring-derived micro vascular cavities, P<0.001. ③ Compared with Normal control subgroup, LHVS subgroup, E64d subgroup and GM6001 subgroup had suppressed micro vascular cavity formation, all P<0.05.④ Aortic ring-derived micro vascular cavity was composed by endothelial cells. Conclusion: CatS plays a beneficial role in ischemic vascular regeneration in experimental mice; it is not only increasing aortic ring-derived micro vascular cavity formation, but also promoting blood flow recovery in ischemic hindlimb. Our finding provides a theoretical basis for new therapeutic target in ischemic vascular regeneration.
ABSTRACT
Objective: To investigate the impact of cathepsins S (CatS) on aortic ring-derived micro vascular cavity formation in experimental mice. Methods: Hindlimb ischemia model was established in CatS+/+ and CatS-/- mice, n=8 in each group. The blood flow in hindlimb was measured before ischemic surgery; immediately and 1, 4, 7, 14, 21 days after surgery. CatS+/+mice were further divided into 4 subgroups: Normal control subgroup, Selective CatS inhibitor (LHVS) subgroup, Non-selective CatS inhibitor (E64d) subgroup and MMP inhibitor (GM6001) subgroup; n=2 in each subgroup. The mice aortic ring-derived micro vascular cavity formation was observed by FITC-CD31 immunofluorescence method. Results: ① CatS-/- mice had inhibited blood flow recovery after ischemic surgery. Laser Doppler blood flow (LDBF) examination indicated that compared with CatS+/+group, CatS-/- group had slower hindlimb blood flow recovery, P<0.05;② CatS-/-group had the less aortic ring-derived micro vascular cavities, P<0.001. ③ Compared with Normal control subgroup, LHVS subgroup, E64d subgroup and GM6001 subgroup had suppressed micro vascular cavity formation, all P<0.05.④ Aortic ring-derived micro vascular cavity was composed by endothelial cells. Conclusion: CatS plays a beneficial role in ischemic vascular regeneration in experimental mice; it is not only increasing aortic ring-derived micro vascular cavity formation, but also promoting blood flow recovery in ischemic hindlimb. Our finding provides a theoretical basis for new therapeutic target in ischemic vascular regeneration.