Diet-induced obesity drives negative mouse vein graft wall remodeling.

Abstract

INTRODUCTION:

The heightened inflammatory phenotype associated with obesity has been linked to the development of cardiovascular diseases. Short-term high-fat feeding induces a proinflammatory state that may impact the blood vessel wall. CD11c, a significantly increased dendritic cell biomarker during diet-induced obesity (DIO), may have a mechanistic role in this high-fat feeding effect. We hypothesized that the proinflammatory effect of short-term DIO accelerates vein bypass graft failure via CD11c-dependent mechanisms.

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.

• Authors: Peng Yu, Binh T Nguyen, Ming Tao, Tianyu Jiang, C Keith Ozaki
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 59 Issue 6 Pg. 1670-6 (Jun 2014) ISSN: 1097-6809 [Electronic] United States
• PMID: 23876511 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Chemical References

• Dietary Fats

Topics

• Animals
• Carotid Stenosis (surgery)
• Dietary Fats (adverse effects)
• Disease Models, Animal
• Graft Occlusion, Vascular (etiology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (complications, surgery)
• Vena Cava, Inferior (pathology, transplantation)