title: Hyperhomocysteinemia inhibits post-injury reendothelialization in mice.
abstract: OBJECTIVE
  Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease and has been reported to inhibit endothelial cell (EC) growth. Notwithstanding, precisely how HHcy regulates EC growth in vivo remains unknown. In this study, we established a mouse model of endothelial injury and reendothelialization and examined the role and mechanism of HHcy in endothelial repair.
  
  
  RESULTS
  A mouse model of carotid artery air-dry endothelium denudation and reendothelialization was established and used to evaluate post-injury endothelial repair in mice with the gene deletion of cystathionine-beta-synthase (CBS). Moderate and severe HHcy were induced in CBS+/+ and CBS-/+ mice through a high-methionine diet. Post-injury reendothelialization, which correlated with increased post-injury neointima formation, was impaired in severe HHcy mice. To elucidate the underlying mechanism, we examined circulating endothelial progenitor cells (EPC) in HHcy mice and studied the effect of homocysteine (Hcy) on proliferation, migration, and adhesion of human umbilical vein endothelial cells (HUVEC). The peripheral EPC population was not significantly altered in HHcy mice. Hcy had a profound inhibitory effect on EC proliferation and migration at physiologically relevant concentrations and inhibited EC adhesion at concentrations of 200 microM and higher.
  
  
  CONCLUSIONS
  We have established a convenient and accurate mouse model of carotid injury in which the reendothelialization process can be precisely quantified. In addition, we have observed impaired reendothelialization and increased neointimal formation in severe HHcy mice. The capacity of Hcy to inhibit proliferation and migration of EC may be responsible for impaired reendothelialization and contribute to arteriosclerosis in HHcy.
authors.affiliation: Department of Medicine, Baylor College of Medicine, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Tan
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Liao
authors.forename: JoAnn
authors.initials: J
authors.lastname: Trial
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Magera
authors.forename: William
authors.initials: W
authors.lastname: Durante
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003541:Cystathionine beta-Synthase / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D012038:Regeneration; D013234:Stem Cells / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology; D014471:Umbilical Veins / Q000166:cytology; D014945:Wound Healing
chemical_list: D006710:Homocysteine; D003541:Cystathionine beta-Synthase