title: Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice.
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.
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Chengwei
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lavelle
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Caijia
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002339:Carotid Arteries / Q000378:metabolism / Q000601:surgery*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism*; D007601:Jugular Veins / Q000378:metabolism / Q000637:transplantation*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D058426:Neointima / Q000235:genetics / Q000378:metabolism; D051381:Rats; D066253:Vascular Remodeling
chemical_list: D006710:Homocysteine; D003094:Collagen; D004549:Elastin; D017493:Leukocyte Common Antigens; D003541:Cystathionine beta-Synthase