title: Enhanced Rho-kinase activity in circulating neutrophils of patients with vasospastic angina: a possible biomarker for diagnosis and disease activity assessment.
abstract: OBJECTIVE
  The aim of this study was to examine whether Rho-kinase activity is systemically enhanced in patients with vasospastic angina (VSA) and, if so, whether a noninvasive diagnostic method could be developed to improve practice.
  
  
  BACKGROUND
  The activated Rho-kinase pathway plays a central role in the molecular mechanism of coronary vasospasm in animal models and patients with VSA. Recently, it has been reported that Rho-kinase activity in circulating leukocytes is associated with various diseases.
  
  
  METHODS
  Fifty-three consecutive patients with chest pain who underwent acetylcholine provocation testing for coronary spasm were examined. Patients were divided into 2 groups depending on their response to the test: VSA (n = 33) and non-VSA (n = 20) groups. Venous blood samples were collected to measure Rho-kinase activity in circulating neutrophils, determined by the extent of phosphorylation of myosin-binding subunit (MBS), a substrate of Rho-kinase.
  
  
  RESULTS
  Rho-kinase activity was significantly higher in the VSA group than in the non-VSA group (phosphorylated MBS/total MBS ratio 1.33 ± 0.37 vs. 0.95 ± 0.22, p < 0.001). In the VSA group, no correlation was noted between Rho-kinase activity and high-sensitivity C-reactive protein, smoking, or accumulated number of coronary risk factors. After the 3-month medical treatment, Rho-kinase activity in the VSA group was significantly decreased to 1.08 ± 0.31 (p < 0.001). On receiver-operating characteristic curve analysis, a phosphorylated MBS ratio of 1.18 was identified as the best cutoff level to predict the diagnosis of VSA.
  
  
  CONCLUSIONS
  These results indicate that Rho-kinase activity in circulating neutrophils is enhanced in patients with VSA and may be a useful biomarker for diagnosis and disease activity assessment of the vasospastic disorder.
authors: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yoku
authors: Y
authors: Kikuchi
authors: Satoshi
authors: S
authors: Yasuda
authors: Kentaro
authors: K
authors: Aizawa
authors: Ryuji
authors: R
authors: Tsuburaya
authors: Yoshitaka
authors: Y
authors: Ito
authors: Morihiko
authors: M
authors: Takeda
authors: Masaharu
authors: M
authors: Nakayama
authors: Kenta
authors: K
authors: Ito
authors: Jun
authors: J
authors: Takahashi
authors: Hiroaki
authors: H
authors: Shimokawa
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D003329:Coronary Vasospasm / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000032:analysis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D054460:rho-Associated Kinases