Circadian Variation of Rho-Kinase Activity in Circulating Leukocytes of Patients With Vasospastic Angina

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  • Nihei Taro
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Takahashi Jun
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Tsuburaya Ryuji
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Ito Yoshitaka
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Shiroto Takashi
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Hao Kiyotaka
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Takagi Yusuke
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Matsumoto Yasuharu
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Nakayama Masaharu
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Miyata Satoshi
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Sakata Yasuhiko
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Ito Kenta
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
  • Shimokawa Hiroaki
    Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

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Abstract

Background: Vasospastic angina (VSA) is known to exhibit circadian variation with an early morning peak. We examined whether Rho-kinase activity in circulating leukocytes, which is a useful biomarker for disease activity assessment of VSA, exhibits circadian variation in patients with VSA. Methods and Results: In consecutive 31 VSA patients (M/F 23/8, 57±13 [SD] years) and 18 non-VSA patients (M/F 8/10, 57±14 years), we measured Rho-kinase activity in circulating leukocytes at 6:00, 12:00 and 21:00. We also examined the relationship between the Rho-kinase activity and coronary vasomotor responses during provocation test. Rho-kinase activity was significantly higher in VSA patients than in non-VSA patients at 6:00 (1.17±0.17 vs. 0.92±0.22, P<0.001), and showed a significant circadian variation with a peak at 6:00 (1.00±0.15 at 21:00, 1.17±0.17 at 6:00 and 1.12±0.22 at 12:00, P<0.001) in VSA patients, whereas no such variation was noted in non-VSA patients. Importantly, Rho-kinase activity at spasm provocation test was significantly correlated with basal coronary tone defined by vasodilating responses to intracoronary nitrate (r=0.40, P<0.05) and coronary vasoconstricting responses to acetylcholine (r=0.44, P<0.05) in VSA patients. Furthermore, their Rho-kinase activity at 6:00 was positively correlated with nocturnal parasympathetic activity as evaluated by heart rate variability in Holter monitoring (r=0.48, P<0.05). Conclusions: Rho-kinase activity exhibits distinct circadian variation associated with alterations in coronary vasomotor responses and autonomic activity in VSA patients.  (Circ J 2014; 78: 1183–1190)<br>

Journal

  • Circulation Journal

    Circulation Journal 78 (5), 1183-1190, 2014

    The Japanese Circulation Society

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