Pontificia Universidad Católica de Chile, Escuela de Medicina, Departamento De Enfermedades Cardiovasculares, Santiago, Chile.
Am Heart J. 2011 May;161(5):931-7. doi: 10.1016/j.ahj.2011.01.024.
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.
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).
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).
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.
小 G 蛋白 Rho 及其靶标 Rho 激酶在实验性重构和心室功能障碍中具有重要作用，但心力衰竭（HF）患者中 Rho 激酶激活的数据尚不清楚。我们假设，在慢性 HF 患者中，循环白细胞中的 Rho 激酶被激活，并与左心室（LV）重构和功能障碍相关。
因此，我们比较了因收缩功能障碍而处于纽约心脏协会（NYHA）功能 II 或 III 级的 HF 患者（n = 17）、健康对照者（n = 17）和无 HF 的高血压患者（n = 17）的循环白细胞中 Rho-激酶活性（通过循环白细胞中磷酸化肌球蛋白轻链磷酸酶 1（MYPT1-P/T）的水平评估）和超声心动图 LV 功能数据。
在对照组中，平均 MYPT1-P/T 比值为 1.2 ± 0.2（无 HF 的高血压患者中相似），而 HF 患者中该比值显著增加了 >100 倍（P <.001）。MYPT1-P/T 和 log MYPT1-P/T 比值均与射血分数呈负相关（r = -0.54，P <.03 和 r = -0.86，P <.001）。此外，在 LV 舒张末期直径 <60 mm 的 HF 患者中，MYPT1-P/T 比值为 35.8 ± 18.1，而在 LV 直径≥60 mm 的患者中，该比值显著更高（P <.05）。
在接受最佳药物治疗的稳定慢性 HF 患者中，Rho 激酶活性显著增加，并且与病理性 LV 重构和收缩功能障碍相关。HF 患者中 Rho 激酶激活的机制、其在疾病进展中的作用以及 Rho 激酶抑制的直接作用需要进一步研究。
