Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Heart Failure
Rho-Kinase Activation in Patients With Heart Failure
Zhulanqiqige Do.e, Yoshihiro Fukumoto, Koichiro Sugimura, Yutaka Miura, Shunsuke Tatebe, Saori Yamamoto, Tatsuo Aoki, Kotaro Nochioka, Suvd Nergui, Nobuhiro Yaoita, Kimio Satoh, Masateru Kondo, Makoto Nakano, Yuji Wakayama, Koji Fukuda, Taro Nihei, Yoku Kikuchi, Jun Takahashi, Hiroaki Shimokawa
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Keywords: Biomarker, Circulating leukocytes, Heart failure, Myocardial biopsy, Rho-Kinase
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2013 Volume 77 Issue 10 Pages 2542-2550

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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. Methods and 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.  (Circ J 2013; 77: 2542–2550)

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© 2013 THE JAPANESE CIRCULATION SOCIETY
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