Artículo de revista
Markedly increased Rho-kinase activity in circulating leukocytes in patients with chronic heart failure
Fecha
2011-05Registro en:
AMERICAN HEART JOURNAL Volume: 161 Issue: 5 Pages: 931-937 Published: MAY 2011
0002-8703
DOI: 10.1016/j.ahj.2011.01.024
Autor
Ocaranza, María Paz
Gabrielli, Luigi
Mora, Italo
García Nannig, Lorena
McNab, Paul
Godoy, Iván
Braun, Sandra
Córdova, Samuel
Castro, Pablo
Novoa, Ulises
Chiong Lay, Mario
Lavandero González, Sergio
Jalil, E.
Institución
Resumen
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.