Diet-induced obesity drives negative mouse vein graft wall remodeling

饮食引起的肥胖会导致小鼠静脉移植壁重塑

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作者:Peng Yu, Binh T Nguyen, Ming Tao, Tianyu Jiang, C Keith Ozaki

Conclusions

These findings highlight negative wall remodeling as a potential factor leading to vein graft failure and provide direct evidence that short-term dietary alterations in the mammalian metabolic milieu can have lasting implications related to acute vascular interventions. DIO induces negative mouse vein graft wall remodeling via CD11c-depedent pathways.

Methods

Male 9-week-old DIO mice (n = 13, C57BL/6J recipients; n = 6, CD11c(-/-) recipients) and normal chow controls (n = 15, C57BL/6J recipients; n = 6, CD11c(-/-) recipients) underwent unilateral carotid interposition vein isografting (inferior vena cava from the same diet and genetic background donor), with a midgraft or outflow focal stenosis. Vein grafts were harvested at either 1 week (immunohistochemical staining for early CD11c expression) or 4 weeks later (morphometric analyses and CD11c evaluation).

Results

Despite a 40% larger body size, C57BL/6J DIO mice had 44% smaller poststenosis vein graft lumens (P = .03) than their controls via an acceleration of overall negative vein graft wall remodeling in the day-28 midgraft focal stenosis model but not in the outflow stenosis model. Higher CD11c expression occurred in DIO midgraft-stenosis vein graft walls, both at postoperative days 7 and 28. In contrast, with in vivo CD11c deficiency, DIO did not elicit this poststenotic negative remodeling but attenuated intimal hyperplasia. Conclusions: These findings highlight negative wall remodeling as a potential factor leading to vein graft failure and provide direct evidence that short-term dietary alterations in the mammalian metabolic milieu can have lasting implications related to acute vascular interventions. DIO induces negative mouse vein graft wall remodeling via CD11c-depedent pathways.

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