Loss of c-Kit in Endothelial Cells Protects against Hindlimb Ischemia.
Biomedicines
; 12(6)2024 Jun 19.
Article
in En
| MEDLINE
| ID: mdl-38927565
ABSTRACT
BACKGROUND:
Critical limb ischemia (CLI) is the end stage of peripheral artery disease (PAD), and around 30% of CLI patients are ineligible for current treatments. The angiogenic benefits of c-Kit have been reported in the ischemia scenario; however, the present study demonstrates the effects of specific endothelial c-Kit signaling in arteriogenesis during hindlimb ischemia.METHODS:
We created conditional knockout mouse models that decrease c-Kit (c-Kit VE-Cadherin CreERT2-c-Kit) or its ligand (SCF VE-Cadherin CreERT2-SCF) specifically in endothelial cells (ECs) after tamoxifen treatment. These mice and a control group (wild-type VE-Cadherin CreERT2-WT) were subjected to hindlimb ischemia or aortic crush to evaluate perfusion/arteriogenesis and endothelial barrier permeability, respectively.RESULTS:
Our data confirmed the lower gene expression of c-Kit and SCF in the ECs of c-Kit and SCF mice, respectively. In addition, we confirmed the lower percentage of ECs positive for c-Kit in c-Kit mice. Further, we found that c-Kit and SCF mice had better limb perfusion and arteriogenesis compared to WT mice. We also demonstrated that c-Kit and SCF mice had a preserved endothelial barrier after aortic crush compared to WT.CONCLUSIONS:
Our data demonstrate the deleterious effects of endothelial SCF/c-Kit signaling on arteriogenesis and endothelial barrier integrity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Biomedicines
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Suiza