Open Access
Article
Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice
Hongmei Tan1,*,Chengwei Shi2,Xiaohua Jiang3,Muriel Lavelle3,Caijia Yu3,Xiaofeng Yang3,4,5,6,Hong Wang3,4,5,6
1
Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China 510080, USA
2
Novartis Pharmaceuticals Corporation, East Hanover, NJ, 07936, USA
3
USA Centers for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PA, 19140, USA
4
Cardiovascular Research, Temple University School of Medicine, Philadelphia, PA, 19140, USA
5
Thrombosis Research, Temple University School of Medicine, Philadelphia, PA, 19140, USA
6
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, 19140, USA
DOI: 10.2741/4260 Volume 19 Issue 6, pp.958-966
Published: 01 June 2014
*Corresponding Author(s):  
Hongmei Tan
E-mail:  
tanhm@mail.sysu.edu.cn
Abstract

This study investigated the role and mechanism of Hyperhomocysteinemia (HHcy) on vascular remodeling in mice. We assessed the effect of HHcy on vascular remodeling using a carotid arterial vein patch model in mice with the gene deletion of cystathionine-beta-synthase (Cbs). Vein grafts were harvested 4 weeks after surgery. Cross sections were analyzed using Verhoeff-van Gieson staining, Masson’s Trichrome staining, and immunostaining for morphological analysis and protein level assessment. The effect of Hcy on collagen secretion was examined in cultured rat aortic smooth muscle cells (RASMC). We found that Cbs-/- mice with severe HHcy exhibited thicker neointima and a higher percentage of luminal narrowing in vein grafts. In addition, severe HHcy increased elastin and collagen deposition in the neointima. Further, severe HHcy increases CD45 positive cells and proliferative cells in vein grafts. Finally, Hcy increases collagen secretion in RASMC. These results demonstrate that HHcy increases neointima formation, elastin and collagen deposition following a carotid arterial vein patch. The capacity of Hcy to promote vascular fibrosis and inflammation may contribute to the development of vascular remodeling.

Key words

Atherosclerosis, Homocysteine, Smooth Muscle Cell, Collagen

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Hongmei Tan, Chengwei Shi, Xiaohua Jiang, Muriel Lavelle, Caijia Yu, Xiaofeng Yang, Hong Wang. Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice. Frontiers in Bioscience-Landmark. 2014. 19(6); 958-966.