title: Circadian variation of Rho-kinase activity in circulating leukocytes of patients with vasospastic angina.
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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
authors.forename: Taro
authors.initials: T
authors.lastname: Nihei
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Tsuburaya
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiroto
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Hao
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takagi
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyata
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sakata
authors.forename: Kenta
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000201:enzymology* / Q000503:physiopathology*; D002940:Circadian Rhythm; D005260:Female; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000097:blood*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human