title: Lack of interleukin-1 signaling results in perturbed early vein graft wall adaptations.
abstract: BACKGROUND
  Vein grafts fail as the result of wall maladaptations to surgical injury and hemodynamic perturbations. Interleukin-1 signaling has emerged as an important mediator of the vascular response to trauma and hemodynamically induced vascular lesions. We therefore hypothesized that interleukin-1 signaling drives early vein graft wall adaptations.
  
  
  METHODS
  Using interleukin-1 type I receptor knockout (IL-1RI(-/-)) and wild-type (B6129SF2/J) mice, we investigated morphologic changes 28 days after interposition isograft from donor inferior vena cava to recipient carotid artery, without (n = 19) or with (n = 13) outflow restriction. The impact of mouse strain on the response to vein arterialization also was evaluated between B6129SF2/J (n = 18) and C57BL/6J (n = 19) mice.
  
  
  RESULTS
  No differences were observed in the traditional end points of intimal thickness and calculated luminal area, yet media+adventitia thickness of the vein graft wall of IL-1RI(-/-) mice was 44% to 52% less than wild-type mice, at the both proximal (P < .01, P < .01) and distal (P = .054, P < .01) portions of vein grafts, for both normal flow and low flow, respectively. Compared with the C57BL/6J strain, B6129SF2/J mice exhibited no difference in vein graft intimal thickness but 2-fold greater media+adventitia thickness (P < .01).
  
  
  CONCLUSIONS
  When lacking IL-1 signaling, the vein graft wall adapts differently compared with the injured artery, showing typical intima hyperplasia although attenuated media+adventitia thickening. B6129SF2/J mice exhibit more media+adventitia response than C57BL/6J mice. The inflammatory networks that underlie the vein response to arterialization hold many roles in the adaptation of the total wall; thus, the utility of anti-inflammatory approaches to extend the durability of vein grafts comes into question.
authors.affiliation: Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.forename: Binh T
authors.initials: BT
authors.lastname: Nguyen
authors.forename: Ming
authors.initials: M
authors.lastname: Tao
authors.forename: Tianyu
authors.initials: T
authors.lastname: Jiang
authors.forename: Christine R
authors.initials: CR
authors.lastname: Mauro
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.forename: C Keith
authors.initials: CK
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017536:Carotid Artery, Common / Q000601:surgery*; D006965:Hyperplasia; D007375:Interleukin-1 / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D014463:Ultrasonography; D058017:Vascular Grafting; D014682:Vena Cava, Inferior / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
chemical_list: D015415:Biomarkers; D007375:Interleukin-1; D053573:Receptors, Interleukin-1 Type I