Plasma Tetrahydrobiopterin/Dihydrobiopterin Ratio A Possible Marker of Endothelial Dysfunction

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  • Takeda Masafumi
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Yamashita Tomoya
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Shinohara Masakazu
    Division of Cardiovascular Medicine, Department of Internal Medicine, The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine
  • Sasaki Naoto
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Takaya Tomofumi
    Department of Cardiovascular Medicine, Nakatsu Saiseikai Hospital
  • Nakajima Kenji
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Inoue Nobutaka
    Department of Vascular Physiology, National Cardiovascular Center Research Institute
  • Masano Tomoya
    Department of General Medicine, Nakatsu Saiseikai Hospital
  • Tawa Hideto
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Satomi-Kobayashi Seimi
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Toh Ryuji
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Sugiyama Daisuke
    Department of Evidence-Based Laboratory Medicine, Kobe University Graduate School of Medicine
  • Nishimura Kunihiro
    Department of Evidence-Based Laboratory Medicine, Kobe University Graduate School of Medicine
  • Yokoyama Mitsuhiro
    Department of Cardiovascular Medicine, Awaji Prefectural Hospital
  • Hirata Ken-ichi
    Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine
  • Kawashima Seinosuke
    Department of General Medicine, Nakatsu Saiseikai Hospital

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  • A Possible Marker of Endothelial Dysfunction

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Abstract

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. (Circ J 2009; 73: 955 - 962)<br>

Journal

  • Circulation Journal

    Circulation Journal 73 (5), 955-962, 2009

    The Japanese Circulation Society

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