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Heart and vessels
Jan, 2019;34 (1): 1-8.

Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm.

Ken Watanabe, Tetsuro Shishido, Yoichiro Otaki, Tetsu Watanabe, Takayuki Sugai, Taku Toshima, Tetsuya Takahashi, Miyuki Yokoyama, Daisuke Kinoshita, Takayo Murase, Takashi Nakamura, Masahiro Wanezaki, Harutoshi Tamura, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, So Yamauchi, Tamon Yamanaka, Takuya Miyamoto, Isao Kubota, Masafumi Watanabe
Author Information
  1. Ken Watanabe: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  2. Tetsuro Shishido: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan. tshishid@med.id.yamagata-u.ac.jp.
  3. Yoichiro Otaki: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  4. Tetsu Watanabe: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  5. Takayuki Sugai: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  6. Taku Toshima: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  7. Tetsuya Takahashi: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  8. Miyuki Yokoyama: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  9. Daisuke Kinoshita: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  10. Takayo Murase: Radioisotope and Chemical Analysis Center, Sanwa Kagaku Kenkyusho Co., Ltd, Mie, Japan.
  11. Takashi Nakamura: Pharmacological Study Group, Pharmaceutical Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd, Mie, Japan.
  12. Masahiro Wanezaki: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  13. Harutoshi Tamura: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  14. Satoshi Nishiyama: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  15. Hiroki Takahashi: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  16. Takanori Arimoto: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  17. So Yamauchi: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  18. Tamon Yamanaka: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  19. Takuya Miyamoto: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  20. Isao Kubota: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
  21. Masafumi Watanabe: Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
PMID: 29936631 DOI: 10.1007/s00380-018-1207-4

Abstract

Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.

Keywords

Coronary artery spasm Reactive oxygen species Uric acid Xanthine oxidoreductase

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Grants

  1. 17K15984/KAKENHI
  2. 25461039/KAKENHI
  3. 18K08025/KAKENHI
  4. 18K08059/KAKENHI

MeSH Term

Aged
Biomarkers
Coronary Angiography
Coronary Vasospasm
Coronary Vessels
Female
Humans
Male
Middle Aged
Oxidation-Reduction
Xanthine Dehydrogenase

Chemicals

Biomarkers
Xanthine Dehydrogenase
Comparative Study Journal Article

Word Cloud

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