Rho-Kinase Activation in Patients With Heart Failure

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Author(s)

    • DO.E Zhulanqiqige
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • FUKUMOTO Yoshihiro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • SUGIMURA Koichiro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • MIURA Yutaka
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • TATEBE Shunsuke
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • YAMAMOTO Saori
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • AOKI Tatsuo
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • NOCHIOKA Kotaro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • NERGUI Suvd
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • YAOITA Nobuhiro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • SATOH Kimio
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • KONDO Masateru
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • NAKANO Makoto
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • WAKAYAMA Yuji
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • FUKUDA Koji
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • NIHEI Taro
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • KIKUCHI Yoku
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • TAKAHASHI Jun
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
    • SHIMOKAWA Hiroaki
    • Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine

Abstract

<b><i>Background:</i></b> 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. <b><i>Methods and Results:</i></b> 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. <b><i>Conclusions:</i></b> Rho-kinase is activated in HF patients, suggesting that it could be a new therapeutic target of the disorder.  (<i>Circ J</i> 2013; <b>77:</b> 2542–2550)<br>

Journal

  • Circulation Journal

    Circulation Journal 77(10), 2542-2550, 2013-09-25

    The Japanese Circulation Society

References:  46

Cited by:  1

Codes

  • NII Article ID (NAID)
    10031191794
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13469843
  • Data Source
    CJP  CJPref  J-STAGE 
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