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

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• 作者：Marí ; a Paz Ocaranza PhD^a ; Luigi Gabrielli MD^a ; ^{lgabriel@med.puc.cl"" rel=""nofollow} ; Italo Mora Bq^a ; Lorena Garcia PhD^b ; ^c ; ^d ; Paul McNab MD^a ; Ivá ; n Godoy MD^a ; Sandra Braun MD^a ; Samuel Có ; rdova MD^a ; Pablo Castro MD^a ; Ulises Novoa PhD^a ; Mario Chiong PhD^b ; ^c ; ^d ; Sergio Lavandero PhD^b ; ^c ; ^d ; ^e ; Jorge E. Jalil MD^a ; ^{jjalil@med.puc.cl"" rel=""nofollow}
• 刊名：American Heart Journal
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：161
• 期：5
• 页码：931-937
• 全文大小：287 K

文摘

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.