title: Oral administration of tetrahydrobiopterin slows the progression of atherosclerosis in apolipoprotein E-knockout mice.
abstract: OBJECTIVE
  Although it has been reported that oral administration of tetrahydrobiopterin (BH4) prevents endothelial dysfunction and vascular oxidative stress in various rat models, the effect of treatment with BH4 on atherogenesis remains unclear.
  
  
  RESULTS
  In this study, we investigated whether oral BH4 treatment might slow the progression of atherosclerosis using hypercholesterolemic apolipoprotein E-knockout mice. We report that ingesting BH4 in drinking water is sufficient to inhibit atherogenesis in mice. Furthermore, we report that BH4 treatment improves endothelial dysfunction and attenuates increased mRNA expression of NADPH oxidase components, as well as a number of inflammatory factors, such as LOX-1 and MCP-1, in the aortas of apolipoprotein E- knockout mice.
  
  
  CONCLUSIONS
  Strategies such as oral administration of BH4 to ensure continuous BH4 availability may be effective in restoring nitric oxide-mediated endothelial function and limiting vascular disease and the progression of atherosclerosis.
authors.affiliation: Department of Endocrinology & Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. yhattori@dokkyomed.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hattori
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Satoh
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Kasai
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006937:Hypercholesterolemia / Q000150:complications; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D013481:Superoxides / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013481:Superoxides; D001708:Biopterins; C003402:sapropterin