title: Markedly increased Rho-kinase activity in circulating leukocytes in patients with chronic heart failure.
abstract: BACKGROUND
  The small guanosine triphosphatase Rho and its target Rho-kinase have significant roles in experimental remodeling and ventricular dysfunction, but no data are available on Rho-kinase activation in patients with heart failure (HF). We hypothesized that, in patients with chronic HF, Rho-kinase in circulating leukocytes is activated and related to left ventricular (LV) remodeling and dysfunction.
  
  
  METHODS
  Accordingly, Rho-kinase activity, assessed by the levels of phosphorylated to total myosin light chain phosphatase 1 (MYPT1-P/T) in circulating leukocytes, and echocardiographic LV function data were compared between patients with HF New York Heart Association functional class II or III due to systolic dysfunction (n = 17), healthy controls (n = 17), and hypertensive patients without HF (n = 17).
  
  
  RESULTS
  In the control subjects, mean MYPT1-P/T ratio was 1.2 ± 0.2 (it was similar in the hypertensive patients without HF), whereas in patients with HF, it was significantly increased by >100-fold (P < .001). Both MYPT1-P/T and log MYPT1-P/T ratios were inversely correlated with ejection fraction (r = -0.54, P < .03 and r = -0.86, P < .001, respectively). Furthermore, in patients with HF with LV end-diastolic diameter <60 mm, MYPT1-P/T ratio was 35.8 ± 18.1, whereas it was significantly higher in patients with LV diameter ≥60 mm (P < .05).
  
  
  CONCLUSIONS
  Rho-Kinase activity is markedly increased in patients with stable chronic HF under optimal medical treatment, and it is associated with pathologic LV remodeling and systolic dysfunction. Mechanisms of Rho-kinase activation in patients with HF, its role in the progression of the disease, and the direct effect of Rho-kinase inhibition need further investigation.
authors.affiliation: Pontificia Universidad Católica de Chile, Escuela de Medicina, Departamento De Enfermedades Cardiovasculares, Santiago, Chile.
authors.forename: María Paz
authors.initials: MP
authors.lastname: Ocaranza
authors.forename: Luigi
authors.initials: L
authors.lastname: Gabrielli
authors.forename: Italo
authors.initials: I
authors.lastname: Mora
authors.forename: Lorena
authors.initials: L
authors.lastname: Garcia
authors.forename: Paul
authors.initials: P
authors.lastname: McNab
authors.forename: Iván
authors.initials: I
authors.lastname: Godoy
authors.forename: Sandra
authors.initials: S
authors.lastname: Braun
authors.forename: Samuel
authors.initials: S
authors.lastname: Córdova
authors.forename: Pablo
authors.initials: P
authors.lastname: Castro
authors.forename: Ulises
authors.initials: U
authors.lastname: Novoa
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.forename: Sergio
authors.initials: S
authors.lastname: Lavandero
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Jalil
mesh_terms: D015153:Blotting, Western; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004452:Echocardiography; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D043263:Myosin-Light-Chain Phosphatase / Q000097:blood; D010766:Phosphorylation; D012720:Severity of Illness Index; D016277:Ventricular Function, Left / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human