title: Increased Rho kinase activity in congestive heart failure.
abstract: OBJECTIVE
  Rho kinases (ROCKs) are the best characterized effectors of the small G-protein RhoA, and play a role in enhanced vasoconstriction in animal models of congestive heart failure (CHF). This study examined if ROCK activity is increased in CHF and how it is associated with the outcome in CHF.
  
  
  RESULTS
  Patients admitted with CHF (n =178), disease controls (n =31), and normal subjects (n =30) were studied. Baseline ROCK activity was measured by phosphorylation of themyosin-binding subunit in peripheral leucocytes. The patients were followed up for 14.4 ± 7.2 months (range 0.5-26 months) or until the occurrence of cardiac death. The ROCK activity in CHF patients (2.93 ± 0.87) was significantly higher than that of the disease control (2.06 ± 0.38, P < 0.001) and normal control (1.57 ± 0.43, P < 0.001) groups. Similarly, protein levels of ROCK1 and ROCK2 as well as the activity of RhoA in CHF were significantly higher than in disease controls and normal controls (all P < 0.05). Dyspnoea at rest (β =0.338, P < 0.001), low left ventricular ejection fraction (β = -0.277, P < 0.001), and high creatinine (β =0.202, P =0.006) were independent predictors of the baseline ROCK activity in CHF. Forty-five patients died within 2 years follow-up (25.3%). Combining ROCK activity and N-terminal pro brain natriuretic peptide (NT-proBNP) had an incremental value (log rank χ(2) =11.62) in predicting long-term mortality when compared with only NT-proBNP (log rank χ(2) =5.16, P < 0.05).
  
  
  CONCLUSIONS
  ROCK activity is increased in CHF and it might be associated with the mortality in CHF. ROCK activity might be a complementary biomarker to CHF risk stratification.
authors.affiliation: Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Alex Pui-Wai
authors.initials: AP
authors.lastname: Lee
authors.forename: Bryan Ping-Yen
authors.initials: BP
authors.lastname: Yan
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Cheuk-Man
authors.initials: CM
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D016022:Case-Control Studies; D004417:Dyspnea / Q000201:enzymology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000201:enzymology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D013318:Stroke Volume; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C066737:RHOA protein, human; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein