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Loss of c-Kit in Endothelial Cells Protects against Hindlimb Ischemia

Authors :
Gustavo Falero-Diaz
Catarina de A. Barboza
Roberto I. Vazquez-Padron
Omaida C. Velazquez
Roberta M. Lassance-Soares
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.

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