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).

Conclusion: 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.

Fig 1

Morphologic analysis of B6129 background mouse vein graft wall adaptation. (A) Mean intimal thickness. (B) Mean concentric lumen area. (C) Mean media+adventitia thickness. (D) Mean intima/(media+adventitia) thickness ratio. Values are shown as mean ± SEM (error bars).

Fig 2

Representative Masson’s trichrome staining of vein graft models on B6129SF2/J wild type or IL-1R1^−/− mice. Lower panel shows the enlargements of area defined by the black boxes in the upper panel. Solid arrows indicate internal elastic lamina; blank arrows indicate outside boundary of the vein graft wall. Scale bars = 50 μm.