CX3CL1-Fc treatment prevents atherosclerosis in Ldlr KO mice.
Atherosclerosis
CX3CR1
Fractalkine
Inflammation
Ldlr KO
Monocyte adhesion
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
15
06
2018
revised:
16
11
2018
accepted:
29
11
2018
pubmed:
17
12
2018
medline:
26
11
2019
entrez:
17
12
2018
Statut:
ppublish
Résumé
Atherosclerosis is a major cause of cardiovascular disease. Monocyte-endothelial cell interactions are partly mediated by expression of monocyte CX3CR1 and endothelial cell fractalkine (CX3CL1). Interrupting the interaction between this ligand-receptor pair should reduce monocyte binding to the endothelial wall and reduce atherosclerosis. We sought to reduce atherosclerosis by preventing monocyte-endothelial cell interactions through use of a long-acting CX3CR1 agonist. In this study, the chemokine domain of CX3CL1 was fused to the mouse Fc region to generate a long-acting soluble form of CX3CL1 suitable for chronic studies. CX3CL1-Fc or saline was injected twice a week (30 mg/kg) for 4 months into Ldlr knockout (KO) mice on an atherogenic western diet. CX3CL1-Fc-treated Ldlr KO mice showed decreased en face aortic lesion surface area and reduced aortic root lesion size with decreased necrotic core area. Flow cytometry analyses of CX3CL1-Fc-treated aortic wall cell digests revealed a decrease in M1-like polarized macrophages and T cells. Moreover, CX3CL1-Fc administration reduced diet-induced atherosclerosis after switching from an atherogenic to a normal chow diet. In vitro monocyte adhesion studies revealed that CX3CL1-Fc treatment caused fewer monocytes to adhere to a human umbilical vein endothelial cell monolayer. Furthermore, a dorsal window chamber model demonstrated that CX3CL1-Fc treatment decreased in vivo leukocyte adhesion and rolling in live capillaries after short-term ischemia-reperfusion. These results indicate that CX3CL1-Fc can inhibit monocyte/endothelial cell adhesion as well as reduce atherosclerosis.
Identifiants
pubmed: 30553772
pii: S2212-8778(18)30619-7
doi: 10.1016/j.molmet.2018.11.011
pmc: PMC6358552
pii:
doi:
Substances chimiques
Chemokine CX3CL1
0
Immunoglobulin Fc Fragments
0
Receptors, LDL
0
Recombinant Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-101Subventions
Organisme : NIAID NIH HHS
ID : P30 AI036214
Pays : United States
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.
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