Circadian variation of Rho-kinase activity in circulating leukocytes of patients with vasospastic angina

Taro Nihei, Jun Takahashi, Ryuji Tsuburaya, Yoshitaka Ito, Takashi Shiroto, Kiyotaka Hao, Yusuke Takagi, Yasuharu Matsumoto, Masaharu Nakayama, Satoshi Miyata, Yasuhiko Sakata, Kenta Ito, Hiroaki Shimokawa

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30 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1183-1190
Number of pages8
JournalCirculation Journal
Issue number5
Publication statusPublished - 2014


  • Circadian variation
  • Rho-kinase activity
  • Vasospastic angina


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