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 journalArticleAcademicpeer-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 languageEnglish
Article number0170644
Number of pages9
JournalPLOS ONE
Volume12
Issue number2
DOIs
Publication statusPublished - 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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