Enhanced rho-kinase activity in circulating neutrophils of patients with vasospastic angina: A possible biomarker for diagnosis and disease activity assessment

Yoku Kikuchi, Satoshi Yasuda, Kentaro Aizawa, Ryuji Tsuburaya, Yoshitaka Ito, Morihiko Takeda, Masaharu Nakayama, Kenta Ito, Jun Takahashi, Hiroaki Shimokawa

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Objectives: 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.

Original languageEnglish
Pages (from-to)1231-1237
Number of pages7
JournalJournal of the American College of Cardiology
Volume58
Issue number12
DOIs
Publication statusPublished - 2011 Sep 13

Keywords

  • acetylcholine
  • inflammation
  • leukocytes
  • vasospasm

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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