PMID- 24896329 OWN - NLM STAT- MEDLINE DCOM- 20150207 LR - 20220224 IS - 2768-6698 (Electronic) IS - 2768-6698 (Linking) VI - 19 IP - 6 DP - 2014 Jun 1 TI - Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice. PG - 958-66 AB - 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. FAU - Tan, Hongmei AU - Tan H AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. FAU - Shi, Chengwei AU - Shi C AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. FAU - Jiang, Xiaohua AU - Jiang X AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. FAU - Lavelle, Muriel AU - Lavelle M AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. FAU - Yu, Caijia AU - Yu C AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. FAU - Yang, Xiaofeng AU - Yang X AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. FAU - Wang, Hong AU - Wang H AD - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, #74 Zhonshan Road 2, Guangzhou, China 510080. LA - eng GR - HL82774/HL/NHLBI NIH HHS/United States GR - R01 HL108910/HL/NHLBI NIH HHS/United States GR - R01 HL077288/HL/NHLBI NIH HHS/United States GR - HL108910/HL/NHLBI NIH HHS/United States GR - R01 HL117654/HL/NHLBI NIH HHS/United States GR - HL67033/HL/NHLBI NIH HHS/United States GR - R01 HL082774/HL/NHLBI NIH HHS/United States GR - R01 HL110764/HL/NHLBI NIH HHS/United States GR - HL110764/HL/NHLBI NIH HHS/United States GR - HL116917/HL/NHLBI NIH HHS/United States GR - R01 HL094451/HL/NHLBI NIH HHS/United States GR - HL9445/HL/NHLBI NIH HHS/United States GR - F32 HL009445/HL/NHLBI NIH HHS/United States GR - HL77288/HL/NHLBI NIH HHS/United States GR - HL117654/HL/NHLBI NIH HHS/United States GR - R01 HL067033/HL/NHLBI NIH HHS/United States GR - R01 HL116917/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140601 PL - Singapore TA - Front Biosci (Landmark Ed) JT - Frontiers in bioscience (Landmark edition) JID - 101612996 RN - 0LVT1QZ0BA (Homocysteine) RN - 9007-34-5 (Collagen) RN - 9007-58-3 (Elastin) RN - EC 3.1.3.48 (Leukocyte Common Antigens) RN - EC 4.2.1.22 (Cystathionine beta-Synthase) RN - Homocysteinemia SB - IM MH - Animals MH - Blotting, Western MH - Carotid Arteries/metabolism/*surgery MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Collagen/metabolism MH - Cystathionine beta-Synthase/genetics/metabolism MH - Elastin/metabolism MH - Homocysteine/pharmacology MH - Hyperhomocysteinemia/genetics/*metabolism MH - Jugular Veins/metabolism/*transplantation MH - Leukocyte Common Antigens/metabolism MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Muscle, Smooth, Vascular/cytology MH - Myocytes, Smooth Muscle/drug effects/metabolism MH - Neointima/genetics/metabolism MH - Rats MH - *Vascular Remodeling PMC - PMC4331018 MID - NIHMS662419 EDAT- 2014/06/05 06:00 MHDA- 2015/02/11 06:00 PMCR- 2015/02/17 CRDT- 2014/06/05 06:00 PHST- 2014/06/05 06:00 [entrez] PHST- 2014/06/05 06:00 [pubmed] PHST- 2015/02/11 06:00 [medline] PHST- 2015/02/17 00:00 [pmc-release] AID - 4260 [pii] AID - 10.2741/4260 [doi] PST - epublish SO - Front Biosci (Landmark Ed). 2014 Jun 1;19(6):958-66. doi: 10.2741/4260.