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(Circulation. 2001;103:133.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Diet-Induced Hyperhomocysteinemia Exacerbates Neointima Formation in Rat Carotid Arteries After Balloon Injury
From the Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo (H.M., H.K., S.Y., T.S., Y.O., Y.K., R.N.) and the Hospital International Medical Center of Japan (Y.Y.), Tokyo, and the Second Department of Internal Medicine, Faculty of Medicine, Gumma University, Gumma (Y.S.), Japan. Dr H. Kurihara is now at the Division of Integrative Cell Biology, Department of Embryogenesis, Institute of Molecular Embryolosy and Genetics, Kumamoto University, Kumamoto, Japan.
Correspondence to Hiroki Kurihara, MD, Division of Integrative Cell Biology, Department of Embryogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. E-mail kurihara{at}kaiju.medic.kumamoto-u.ac.jp
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.
Methods and 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.
Key Words: homocysteine • balloon injury • endothelium • folate
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