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Loss of c-Kit in Endothelial Cells Protects against Hindlimb Ischemia
- Source :
- Biomedicines, Vol 12, Iss 6, p 1358 (2024)
- Publication Year :
- 2024
- Publisher :
- MDPI AG, 2024.
-
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.
- Subjects :
- c-Kit
SCF
arteriogenesis
endothelial barrier
CLI
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 12
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Biomedicines
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.64ab020aed6245b7a5df7eaf95e1b7ab
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/biomedicines12061358