Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice

• Published in: Frontiers in bioscience Vol. 19; no. 6; p. 958
• Main Authors: Tan, Hongmei, Shi, Chengwei, Jiang, Xiaohua, Lavelle, Muriel, Yu, Caijia, Yang, Xiaofeng, Wang, Hong
• Format: Journal Article
• Language: English
• Published: Singapore 01.06.2014
• Subjects: Animals; Blotting, Western; Carotid Arteries - metabolism; Carotid Arteries - surgery; Cell Proliferation - drug effects; Cells, Cultured; Collagen - metabolism; Cystathionine beta-Synthase - genetics; Cystathionine beta-Synthase - metabolism; Elastin - metabolism; Homocysteine - pharmacology; Hyperhomocysteinemia - genetics; Hyperhomocysteinemia - metabolism; Jugular Veins - metabolism; Jugular Veins - transplantation; Leukocyte Common Antigens - metabolism; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular - cytology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Neointima - genetics; Neointima - metabolism; Rats; Vascular Remodeling
• ISSN: 1093-9946; 2768-6698; 1093-4715
• DOI: 10.2741/4260

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.