Open AccessRole of the CX3C chemokine receptor CX3CR1 in the pathogenesis of atherosclerosis after aortic transplantation
Author(s) -
Zuzanna Rowińska,
Thomas A. Koeppel,
Maryam Sanati,
Hubert Schelzig,
Joachim Jankowski,
Christian Weber,
Alma Zernecke,
Elisa A. Liehn
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0170644
Subject(s) - cx3cr1 , apolipoprotein e , transplantation , cx3cl1 , chemokine , aorta , chemokine receptor , pathology , medicine , biology , cancer research , immunology , inflammation , disease
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 Cx3cr 1 -/- Apoe -/- and Cx3cr 1 +/+ Apoe -/- aortic segments into Apoe -/- mice, as well as Apoe -/- aortic segments into Cx3cr 1 -/- 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 Cx3cr 1 -/- 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.