title: Rho-kinase activation in patients with heart failure.
abstract: BACKGROUND
  Heart failure (HF) is a complex clinical syndrome, resulting from structural and/or functional cardiac disease. The aim of this study was to determine whether the activity of Rho-kinase, which has been identified as an important therapeutic target of cardiovascular disease, is enhanced in HF patients.
  
  
  RESULTS
  Total and phosphorylated forms of myosin binding subunit (t-MBS and p-MBS), a substrate of Rho-kinase, were measured on western blotting in circulating leukocytes, and the p-MBS/t-MBS ratio was defined as an index of systemic Rho-kinase activity. First, during the time-course of acute HF (n=12), Rho-kinase activity was significantly elevated in the acute phase compared to the chronic phase (1.19 ± 0.06 vs. 0.97 ± 0.04, P<0.05). Next, Rho-kinase activity was examined in 30 controls and 130 chronic HF patients (cardiomyopathy, n=57; valvular heart disease, n=35; ischemic heart disease [IHD], n=33; and others, n=5). As compared with the controls, Rho-kinase activity was significantly elevated in the total HF group (1.14 ± 0.02 vs. 0.77 ± 0.05, P<0.0001) and in each underlying heart disease (P<0.05 each). Importantly, in the high-risk non-IHD group, Rho-kinase activity was significantly associated with plasma brain nutriuretic peptide level. Finally, p-MBS was expressed in myocardial biopsy samples (immunohistochemistry) in chronic HF patients (n=36), independent of Rho-kinase activity in leukocytes.
  
  
  CONCLUSIONS
  Rho-kinase is activated in HF patients, suggesting that it could be a new therapeutic target of the disorder.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
authors.forename: Zhulanqiqige
authors.initials: Z
authors.lastname: Do e
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sugimura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tatebe
authors.forename: Saori
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Aoki
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nochioka
authors.forename: Suvd
authors.initials: S
authors.lastname: Nergui
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yaoita
authors.forename: Kimio
authors.initials: K
authors.lastname: Satoh
authors.forename: Masateru
authors.initials: M
authors.lastname: Kondo
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wakayama
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Taro
authors.initials: T
authors.lastname: Nihei
authors.forename: Yoku
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000368:Aged; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D054460:rho-Associated Kinases / Q000097:blood*
chemical_list: D020097:Natriuretic Peptide, Brain; D054460:rho-Associated Kinases