title: Diet-induced hyperhomocysteinemia exacerbates neointima formation in rat carotid arteries after balloon injury.
abstract: BACKGROUND
  Increasing evidence indicates that elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and endothelial dysfunction, although little specific information on the mechanisms responsible for the atherogenic effects of homocysteine or on the in vivo contribution made by hyperhomocysteinemia to atherosclerosis is currently available. Because homocysteine is known to exert a direct inhibitory effect on endothelial cell growth in vitro, we hypothesized that this effect contributes to the progression of atherosclerotic lesions initiated by endothelial damage caused by mechanical injury.
  
  
  RESULTS
  We prepared diet-induced hyperhomocysteinemic rats in which neointima formation after balloon injury to the common carotid artery was assessed. Moderate hyperhomocysteinemia (plasma homocysteine levels 3- to 4-fold higher than control) significantly exacerbated neointima formation. Oral administration of folate, which had a homocysteine-lowering effect, diminished neointima formation induced by moderate hyperhomocysteinemia. Furthermore, the attenuation of reendothelialization was shown in diet-induced hyperhomocysteinemic rats with Evans blue staining.
  
  
  CONCLUSIONS
  Diet-induced hyperhomocysteinemia, even mild to moderate, exacerbates neointima formation after denuding injury, making hyperhomocysteinemia a likely risk factor for postangioplasty restenosis. It may be mediated through an inhibitory effect of homocysteine on reendothelialization. Homocysteine lowering with folate supplementation can effectively ameliorate the detrimental effects of moderate hyperhomocysteinemia. Clinical trials would seem to be warranted.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: H
authors.initials: H
authors.lastname: Kurihara
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Shindo
authors.forename: Y
authors.initials: Y
authors.lastname: Oh-Hashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000284:Administration, Oral; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002340:Carotid Artery Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D003553:Cystine / Q000097:blood; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000097:blood / Q000494:pharmacology; D006710:Homocysteine / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D006710:Homocysteine; D003553:Cystine; D005492:Folic Acid; D008715:Methionine