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

María Paz Ocaranza, Luigi Gabrielli, Italo Mora, Lorena Garcia, Paul McNab, Iván Godoy, Sandra Braun, Samuel Córdova, Pablo Castro, Ulises Novoa, Mario Chiong, Sergio Lavandero, Jorge E. Jalil

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35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)931-937
Number of pages7
JournalAmerican Heart Journal
Volume161
Issue number5
DOIs
Publication statusPublished - May 2011

Bibliographical note

Funding Information:
Supported by grants Fondecyt 1085208 (Chile) to J.J. and FONDAP 15010006 (Chile) to S.L.

Funding Information:
Funding for this study was supported by grants Fondecyt, Chile 1085208 (J.E.J.) and FONDAP, Chile 15010006 (S.L.).

Funding

Supported by grants Fondecyt 1085208 (Chile) to J.J. and FONDAP 15010006 (Chile) to S.L. Funding for this study was supported by grants Fondecyt, Chile 1085208 (J.E.J.) and FONDAP, Chile 15010006 (S.L.).

FundersFunder number
Fondo Nacional de Desarrollo Científico y Tecnológico1085208, FONDAP 15010006
Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias15010006

    ASJC Scopus Subject Areas

    • Cardiology and Cardiovascular Medicine

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