CX3CL1-Fc treatment prevents atherosclerosis in Ldlr KO mice
Objective: 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...
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Book |
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Elsevier,
2019-02-01T00:00:00Z.
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| 001 | doaj_9aa1e09a965d493391f4ff36b42d349a | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Matthew Riopel |e author |
| 700 | 1 | 0 | |a Melanie Vassallo |e author |
| 700 | 1 | 0 | |a Erik Ehinger |e author |
| 700 | 1 | 0 | |a Jennifer Pattison |e author |
| 700 | 1 | 0 | |a Karen Bowden |e author |
| 700 | 1 | 0 | |a Holger Winkels |e author |
| 700 | 1 | 0 | |a Maria Wilson |e author |
| 700 | 1 | 0 | |a Ron de Jong |e author |
| 700 | 1 | 0 | |a Sanjay Patel |e author |
| 700 | 1 | 0 | |a Deepika Balakrishna |e author |
| 700 | 1 | 0 | |a James Bilakovics |e author |
| 700 | 1 | 0 | |a Andrea Fanjul |e author |
| 700 | 1 | 0 | |a Artur Plonowski |e author |
| 700 | 1 | 0 | |a Christopher J. Larson |e author |
| 700 | 1 | 0 | |a Klaus Ley |e author |
| 700 | 1 | 0 | |a Pedro Cabrales |e author |
| 700 | 1 | 0 | |a Joseph L. Witztum |e author |
| 700 | 1 | 0 | |a Jerrold M. Olefsky |e author |
| 700 | 1 | 0 | |a Yun Sok Lee |e author |
| 245 | 0 | 0 | |a CX3CL1-Fc treatment prevents atherosclerosis in Ldlr KO mice |
| 260 | |b Elsevier, |c 2019-02-01T00:00:00Z. | ||
| 500 | |a 2212-8778 | ||
| 500 | |a 10.1016/j.molmet.2018.11.011 | ||
| 520 | |a Objective: 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. Methods: 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. Results: 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. Conclusion: These results indicate that CX3CL1-Fc can inhibit monocyte/endothelial cell adhesion as well as reduce atherosclerosis. Keywords: Fractalkine, CX3CR1, Atherosclerosis, Monocyte adhesion, Inflammation, Ldlr KO | ||
| 546 | |a EN | ||
| 690 | |a Internal medicine | ||
| 690 | |a RC31-1245 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Molecular Metabolism, Vol 20, Iss , Pp 89-101 (2019) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2212877818306197 | |
| 787 | 0 | |n https://doaj.org/toc/2212-8778 | |
| 856 | 4 | 1 | |u https://doaj.org/article/9aa1e09a965d493391f4ff36b42d349a |z Connect to this object online. |