Role of the CX3C chemokine receptor CX3CR1 in the pathogenesis of atherosclerosis after aortic transplantation

Zuzanna Rowinska; Thomas A. Koeppel; Maryam Sanati; Hubert Schelzig; Joachim Jankowski; Christian Weber; Alma Zernecke; Elisa A. Liehn

doi:10.1371/journal.pone.0170644

Role of the CX3C chemokine receptor CX3CR1 in the pathogenesis of atherosclerosis after aortic transplantation

Zuzanna Rowinska^*, Thomas A. Koeppel, Maryam Sanati, Hubert Schelzig, Joachim Jankowski, Christian Weber, Alma Zernecke, Elisa A. Liehn

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Web of Science)

Abstract

Background

The CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells ( SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated.

Methods

We here have orthotopically transplanted infrarenal Cx3cr1(-/-) Apoe(-/-) and Cx3cr1(+/+) Apoe(-/-)aortic segments into Apoe(-/-) mice, as well as Apoe(-/-) aortic segments into Cx3cr1(-/-) Apoe(-/-)mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet.

Results

Transplantation of Cx3cr(-/-) Apoe(-/-) aortic segments into Apoe(-/-) mice resulted in reduced atherosclerotic plaque formation compared to plaque size in Apoe(-/-) or Cx3cr1(-/-) Apoe(-/-) mice after transplantation of Apoe(-/-) aortas. This reduction in lesion formation was associated with reduced numbers of lesional SMCs but not macrophages within the transplanted Cx3cr(-/-) Apoe(-/-) aortic segment. No differences in frequencies of proliferating and apoptotic cells could be observed.

Conclusion

These results indicate that CX3CR1 on resident vessel wall cells plays a key role in atherosclerotic plaque formation in transplanted aortic grafts. Targeting of vascular CX3CL1/ CX3CR1 may therefore be explored as a therapeutic option in vascular transplantation procedures.

Original language	English
Article number	0170644
Number of pages	9
Journal	PLOS ONE
Volume	12
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0170644
Publication status	Published - 24 Feb 2017

Keywords

SMOOTH-MUSCLE-CELLS
ALLOGRAFT-REJECTION
LESION FORMATION
GROWTH-FACTOR
MOUSE MODELS
FRACTALKINE
CX(3)CR1
MICE
ARTERIOSCLEROSIS
ATHEROGENESIS

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10.1371/journal.pone.0170644

Cite this

@article{87501a080b3c4b82a4bc424e357ee903,

title = "Role of the CX3C chemokine receptor CX3CR1 in the pathogenesis of atherosclerosis after aortic transplantation",

abstract = "BackgroundThe CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells ( SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated.MethodsWe here have orthotopically transplanted infrarenal Cx3cr1(-/-) Apoe(-/-) and Cx3cr1(+/+) Apoe(-/-)aortic segments into Apoe(-/-) mice, as well as Apoe(-/-) aortic segments into Cx3cr1(-/-) Apoe(-/-)mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet.ResultsTransplantation of Cx3cr(-/-) Apoe(-/-) aortic segments into Apoe(-/-) mice resulted in reduced atherosclerotic plaque formation compared to plaque size in Apoe(-/-) or Cx3cr1(-/-) Apoe(-/-) mice after transplantation of Apoe(-/-) aortas. This reduction in lesion formation was associated with reduced numbers of lesional SMCs but not macrophages within the transplanted Cx3cr(-/-) Apoe(-/-) aortic segment. No differences in frequencies of proliferating and apoptotic cells could be observed.ConclusionThese results indicate that CX3CR1 on resident vessel wall cells plays a key role in atherosclerotic plaque formation in transplanted aortic grafts. Targeting of vascular CX3CL1/ CX3CR1 may therefore be explored as a therapeutic option in vascular transplantation procedures.",

keywords = "SMOOTH-MUSCLE-CELLS, ALLOGRAFT-REJECTION, LESION FORMATION, GROWTH-FACTOR, MOUSE MODELS, FRACTALKINE, CX(3)CR1, MICE, ARTERIOSCLEROSIS, ATHEROGENESIS",

author = "Zuzanna Rowinska and Koeppel, {Thomas A.} and Maryam Sanati and Hubert Schelzig and Joachim Jankowski and Christian Weber and Alma Zernecke and Liehn, {Elisa A.}",

year = "2017",

month = feb,

day = "24",

doi = "10.1371/journal.pone.0170644",

language = "English",

volume = "12",

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T1 - Role of the CX3C chemokine receptor CX3CR1 in the pathogenesis of atherosclerosis after aortic transplantation

AU - Rowinska, Zuzanna

AU - Koeppel, Thomas A.

AU - Sanati, Maryam

AU - Schelzig, Hubert

AU - Jankowski, Joachim

AU - Weber, Christian

AU - Zernecke, Alma

AU - Liehn, Elisa A.

PY - 2017/2/24

Y1 - 2017/2/24

N2 - BackgroundThe CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells ( SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated.MethodsWe here have orthotopically transplanted infrarenal Cx3cr1(-/-) Apoe(-/-) and Cx3cr1(+/+) Apoe(-/-)aortic segments into Apoe(-/-) mice, as well as Apoe(-/-) aortic segments into Cx3cr1(-/-) Apoe(-/-)mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet.ResultsTransplantation of Cx3cr(-/-) Apoe(-/-) aortic segments into Apoe(-/-) mice resulted in reduced atherosclerotic plaque formation compared to plaque size in Apoe(-/-) or Cx3cr1(-/-) Apoe(-/-) mice after transplantation of Apoe(-/-) aortas. This reduction in lesion formation was associated with reduced numbers of lesional SMCs but not macrophages within the transplanted Cx3cr(-/-) Apoe(-/-) aortic segment. No differences in frequencies of proliferating and apoptotic cells could be observed.ConclusionThese results indicate that CX3CR1 on resident vessel wall cells plays a key role in atherosclerotic plaque formation in transplanted aortic grafts. Targeting of vascular CX3CL1/ CX3CR1 may therefore be explored as a therapeutic option in vascular transplantation procedures.

AB - BackgroundThe CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells ( SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated.MethodsWe here have orthotopically transplanted infrarenal Cx3cr1(-/-) Apoe(-/-) and Cx3cr1(+/+) Apoe(-/-)aortic segments into Apoe(-/-) mice, as well as Apoe(-/-) aortic segments into Cx3cr1(-/-) Apoe(-/-)mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet.ResultsTransplantation of Cx3cr(-/-) Apoe(-/-) aortic segments into Apoe(-/-) mice resulted in reduced atherosclerotic plaque formation compared to plaque size in Apoe(-/-) or Cx3cr1(-/-) Apoe(-/-) mice after transplantation of Apoe(-/-) aortas. This reduction in lesion formation was associated with reduced numbers of lesional SMCs but not macrophages within the transplanted Cx3cr(-/-) Apoe(-/-) aortic segment. No differences in frequencies of proliferating and apoptotic cells could be observed.ConclusionThese results indicate that CX3CR1 on resident vessel wall cells plays a key role in atherosclerotic plaque formation in transplanted aortic grafts. Targeting of vascular CX3CL1/ CX3CR1 may therefore be explored as a therapeutic option in vascular transplantation procedures.

KW - SMOOTH-MUSCLE-CELLS

KW - ALLOGRAFT-REJECTION

KW - LESION FORMATION

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KW - MOUSE MODELS

KW - FRACTALKINE

KW - CX(3)CR1

KW - MICE

KW - ARTERIOSCLEROSIS

KW - ATHEROGENESIS

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DO - 10.1371/journal.pone.0170644

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