Gabrielli Luigi, Winter Jose L, Godoy Ivan, McNab Paul, Padilla Ivonne, Cordova Samuel, Rigotti Paola, Novoa Ulises, Mora Italo, García Lorena, Ocaranza Maria P, Jalil Jorge E
School of Medicine, Department of Cardiovascular Diseases, Laboratories of Cardiology and Molecular Cardiology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Am J Hypertens. 2014 Jun;27(6):838-45. doi: 10.1093/ajh/hpt234. Epub 2013 Dec 21.
There is experimental evidence on the role of Rho-kinase (ROCK) activation in cardiac hypertrophy but no information on its role in human hypertension and left ventricular hypertrophy (LVH). We hypothesized that ROCK activity is higher in hypertensive patients with LVH compared with hypertensive patients without LVH.
We conducted a cross-sectional study comparing untreated hypertensive patients with (n = 41) and without LVH (n = 46) determined by echocardiography with a healthy normotensive control group (n = 51). Measurements included LV mass, dimensions, and function and ROCK activity determined in circulating leukocytes by measuring Western blot levels of phosphorylated to total myosin light chain phosphatase 1 (MYPT1-p/t).
Compared with normotensive subjects, MYPT1-p/t was significantly increased by 4.5-fold in the hypertensive patients without LVH and by 9-fold in the hypertensive patients with LVH. Compared with the hypertension without LVH group, MYPT1-p/t was significantly increased by 2-fold in the hypertension with LVH gorup. In patients with eccentric LVH, the mean MYPT1-p/t ratio was significantly higher by 4-fold compared with hypertensive patients without eccentric LVH. Patients with an E/e' ratio ≥15 (n = 6) showed a higher MYPT1-p/t ratio (by 26%) compared with patients with a lower E/e' ratio (P ≤ 0.01).
ROCK activity is higher in hypertensive patients with LVH compared with hypertensive patients without LVH, and it is further increased when eccentric LVH is present. Thus, in hypertension, ROCK activation is related to pathological cardiac remodeling and might have a role as an LVH marker.
有实验证据表明Rho激酶(ROCK)激活在心肌肥大中起作用,但尚无关于其在人类高血压和左心室肥厚(LVH)中作用的信息。我们假设与无LVH的高血压患者相比,有LVH的高血压患者ROCK活性更高。
我们进行了一项横断面研究,将通过超声心动图确定的有(n = 41)和无LVH(n = 46)的未经治疗的高血压患者与健康的血压正常对照组(n = 51)进行比较。测量包括左心室质量、尺寸和功能,以及通过测量磷酸化与总肌球蛋白轻链磷酸酶1(MYPT1-p/t)的蛋白质印迹水平在循环白细胞中测定的ROCK活性。
与血压正常的受试者相比,无LVH的高血压患者的MYPT1-p/t显著增加4.5倍,有LVH的高血压患者增加9倍。与无LVH的高血压组相比,有LVH的高血压组的MYPT1-p/t显著增加2倍。在有离心性LVH的患者中,平均MYPT1-p/t比值比无离心性LVH的高血压患者显著高4倍。E/e'比值≥15的患者(n = 6)与E/e'比值较低的患者相比,MYPT1-p/t比值更高(高26%)(P≤0.01)。
与无LVH的高血压患者相比,有LVH的高血压患者ROCK活性更高,当存在离心性LVH时其活性进一步增加。因此,在高血压中,ROCK激活与病理性心脏重塑有关,可能作为LVH的一个标志物。