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

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

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

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Título: Markedly increased Rho-kinase activity in circulating leukocytes in patients with chronic heart failure
Autor: Ocaranza, María Paz; Gabrielli, Luigi A.; Mora, Italo; García, Lorena; McNab, Paul; Godoy, Iván; Braun, Sandra; Córdova, Samuel; Castro, Pablo; Novoa, Ulises; Chiong Lay, Mario; Lavandero González, Sergio; Jalil, E.
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.
Descripción: Artículo de publicación ISI
URI: http://www.captura.uchile.cl/handle/2250/13983
Fecha: 2011-05
Cita del item: AMERICAN HEART JOURNAL Volume: 161 Issue: 5 Pages: 931-937 Published: MAY 2011


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