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Markedly increased Rho-kinase activity in circulating leukocytes in patients with chronic heart failure

María Paz Ocaranza1, Luigi Gabrielli, Italo Mora

  • 1Pontificia Universidad Católica de Chile, Escuela de Medicina, Departamento De Enfermedades Cardiovasculares, Santiago, Chile.

American Heart Journal
|May 17, 2011
PubMed

Insights

Rho-kinase activity is significantly elevated in heart failure (HF) patients, correlating with left ventricular (LV) dysfunction and remodeling. This finding suggests Rho-kinase as a potential therapeutic target for HF management.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Rho-kinase plays a role in experimental cardiac remodeling and dysfunction.
  • Limited data exist on Rho-kinase activation in human heart failure (HF).

Purpose of the Study:

  • To investigate Rho-kinase activation in circulating leukocytes of patients with chronic HF.
  • To determine the association between Rho-kinase activity and left ventricular (LV) remodeling and dysfunction in HF patients.

Main Methods:

  • Rho-kinase activity was assessed by measuring phosphorylated to total myosin light chain phosphatase 1 (MYPT1-P/T) ratios in leukocytes.
  • Echocardiographic LV function and dimensions were evaluated.
  • Comparisons were made between HF patients (NYHA class II/III), healthy controls, and hypertensive patients without HF.

Main Results:

  • MYPT1-P/T ratios were significantly increased (>100-fold) in HF patients compared to controls and hypertensive patients without HF.
  • MYPT1-P/T ratios were inversely correlated with ejection fraction and positively correlated with LV end-diastolic diameter in HF patients.
  • Rho-kinase activity was markedly increased in stable chronic HF patients on optimal medical treatment.

Conclusions:

  • Rho-kinase activity is significantly elevated in patients with stable chronic heart failure.
  • Increased Rho-kinase activity is associated with pathological LV remodeling and systolic dysfunction in HF.
  • Further research is needed to explore Rho-kinase activation mechanisms, its role in HF progression, and the effects of inhibition.
Abstract

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