Oral administration of tetrahydrobiopterin slows the progression of atherosclerosis in apolipoprotein E-knockout mice.
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.
Hattori
Yoshiyuki
Y
Department of Endocrinology & Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan. yhattori@dokkyomed.ac.jp
Hattori
Sachiko
S
Wang
Xi
X
Satoh
Hiroko
H
Nakanishi
Nobuo
N
Kasai
Kikuo
K
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
D001057:Apolipoproteins E; D018836:Inflammation Mediators; D012333:RNA, Messenger; D013481:Superoxides; D001708:Biopterins; C003402:sapropterin