TY - JOUR
T1 - Plasma tetrahydrobiopterin/dihydrobiopterin ratio - A possible marker of endothelial dysfunction
AU - Takeda, Masafumi
AU - Yamashita, Tomoya
AU - Shinohara, Masakazu
AU - Sasaki, Naoto
AU - Takaya, Tomofumi
AU - Nakajima, Kenji
AU - Inoue, Nobutaka
AU - Masano, Tomoya
AU - Tawa, Hideto
AU - Satomi-Kobayashi, Seimi
AU - Toh, Ryuji
AU - Sugiyama, Daisuke
AU - Nishimura, Kunihiro
AU - Yokoyama, Mitsuhiro
AU - Hirata, Ken Ichi
AU - Kawashima, Seinosuke
PY - 2009/5
Y1 - 2009/5
N2 - Background: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. Methods and Results: In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients with multiple coronary risk factors. There was a positive relationship between FMD and plasma BH4 levels and a negative relationship between FMD and plasma BH2 levels. Subsequently, a strong positive relationship between FMD and the BH4/BH2 ratio (r=0.585, P<0.0001) was found. Although we did not find any significant relationship between pteridine levels and individual traditional risk factors, the BH4/BH2 ratio in patients with more than 2 risk factors showed significant reductions compared with that in those without risk factors. Statin treatment improved FMD in association with an increase in the plasma BH4/BH2 ratio. Conclusions: Plasma pteridine levels were associated with endothelial dysfunction in cardiovascular disorders.
AB - Background: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. Methods and Results: In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients with multiple coronary risk factors. There was a positive relationship between FMD and plasma BH4 levels and a negative relationship between FMD and plasma BH2 levels. Subsequently, a strong positive relationship between FMD and the BH4/BH2 ratio (r=0.585, P<0.0001) was found. Although we did not find any significant relationship between pteridine levels and individual traditional risk factors, the BH4/BH2 ratio in patients with more than 2 risk factors showed significant reductions compared with that in those without risk factors. Statin treatment improved FMD in association with an increase in the plasma BH4/BH2 ratio. Conclusions: Plasma pteridine levels were associated with endothelial dysfunction in cardiovascular disorders.
KW - Endothelial dysfunction
KW - FMD
KW - Plasma pteridine level
KW - Statin
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U2 - 10.1253/circj.CJ-08-0850
DO - 10.1253/circj.CJ-08-0850
M3 - Article
C2 - 19293532
AN - SCOPUS:65649104427
SN - 1346-9843
VL - 73
SP - 955
EP - 962
JO - Circulation Journal
JF - Circulation Journal
IS - 5
ER -