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.

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.  

• Authors: 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
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 77 Issue 10 Pg. 2542-50 ( 2013) ISSN: 1347-4820 [Electronic] Japan
• PMID: 23883874 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Natriuretic Peptide, Brain
• rho-Associated Kinases

Topics

• Aged
• Chronic Disease
• Female
• Heart Failure (drug therapy, enzymology, physiopathology)
• Humans
• Leukocytes (enzymology)
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• rho-Associated Kinases (blood)