Mouse Strain Differential Neointimal Response in Vein Grafts and Wire-Injured Arteries

Abstract

eointimal hyperplasia is a complication of both balloon angioplasty 1,2 and bypass vein grafting. [3][4][5] Experimental studies in mouse models have indicated several possible sources for the neointimal cells, 6 including circulating (pluripotent) cells with arterial wire/ballooninjury 7,8 and some vein graft models, 9,10 and predominantly local cells with arterial cuff injury 11 and in a modified vein graft model. 12 These differences suggest that more than 1 mechanism may be responsible for neointimal hyperplasia, depending on the initiating cause.In a recent report, Kuhel et al 13 identified mouse strain differences in the neointimal response to simulated balloon injury in the carotid artery, so the present study was done to evaluate neointimal formation after both vein grafting and arterial wire injury, using 2 mouse strains with highly disparate neointimal responses under arterial injury: 13 C57Bl/6 mice which show a low neointimal response, and FVB mice, which have a greater neointimal response. MethodsThe animal protocol was approved by the institutional Animal Care and Use Committee and was in accordance with NIH and AALAC guidelines. Male C57Bl/6 and FVB mice (Harlan Sprague-Dawley, Indianapolis, IN, USA), 8-12-weeks-old, were anesthetized with pentobarbital Circulation Journal Vol.71, October 2007Circ J 2007; 71: 1649 -1652 (Received April 11, 2007 revised manuscript received May 24, 2007; accepted July 2, 2007 Background Neointimal development is seen clinically after both vein grafting and balloon catheterization, but may not represent the same pathology under these 2 conditions. This study compared the degree of neointimal hyperplasia after vein grafting or arterial-injury grafts in 2 strains of mice: C57Bl/6 and FVB. Methods and Results Jugular vein branches were interpositioned as grafts in the femoral artery of syngenicmatched mice, with graft harvest at 30 days. Wire-injured carotid arteries were grafted to the carotid arteries of syngenic-matched mice, with graft harvest at 14 days. Histomorphometry revealed no strain differences in vein grafts in the extent of position-dependent neointimal thickening or lumen cross-sectional area. Both strains showed significantly thicker neointima and less lumen area at the proximal graft site (vs the mid-graft; p<0.05). In contrast, a significantly greater neointimal thickness was found in the wire-injured carotid grafts of FVB mice vs those of C57Bl/6 mice (p<0.05).Conclusions Neointimal formation shows a vessel-dependent, strain-dependent difference, with greater arterial neointimal thickening in FVB mice. These data suggest that different mechanisms operate for arterial-injury-vs vein-graft-associated neointimal development and that the difference has a genetic basis. (Circ J 2007; 71: 1649 -1652)

Tumor Necrosis Factor Receptor-2 Signaling Attenuates Vein Graft Neointima Formation by Promoting Endothelial Recovery

“…33 The apparent discord may result from the relative importance of SMC and EC hyperplasia in these 2 different injury models, or may be attributable to the variable but generally small neointimal hyperplastic response produced by carotid wire injury in the C57BL/6 mouse. 34,35 In contrast to neointimal hyperplasia, medial dimension is increased only in p75 Ϫ/Ϫ graft recipients (Figure 1). We have demonstrated significant infiltration of bone marrow-derived cells of the monocyte/macrophage lineage into the media of arterializing vein grafts.…”

Rationale and practical techniques for mouse models of early vein graft adaptations

“…While there exists limited information on differences in susceptibilities to intimal hyperplasia 38 or negative remodeling in mouse vein graft models, data obtained from arterial studies may serve as a useful baseline. 39, 40…”

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

“…According to several reports investigating differences between mouse strains after femoral or carotid artery injury, FVB/N mice display the highest amount of neointima formation, followed by 129/SvJ, C3H/HeJ, BALB/C, and C57BL/6, respectively. 4,9,10 These characteristics should be considered when composing an experimental plan. The femoral injury model can also be utilized for investigation of inflammatory changes after vascular injury.…”