Increased Rho-Kinase Activity in Hypertensive Patients With Left Ventricular Hypertrophy

Increased Rho-Kinase Activity in Hypertensive Patients With Left Ventricular Hypertrophy
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DOI:
10.1093/ajh/hpt234
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发表时间:
2014-06-01
影响因子:
3.2
通讯作者:
Jalil, Jorge E.
Jalil, Jorge E.
中科院分区:
医学3区
文献类型:
--
作者:
Gabrielli, Luigi;Winter, Jose L.;Jalil, Jorge E.

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背景Rho-Kinase(ROCK)激活在心肌肥厚中的作用有实验证据,但尚无关于其在人类高血压和左心室肥厚(LVH)中的作用的信息。我们假设高血压伴左室肥厚患者的ROCK活性高于无左室肥厚的高血压患者。方法:我们进行了一项横断面研究,比较了41例高血压患者(n=41)和46例无左室肥厚(n=46)的高血压患者与51例正常血压的健康对照组的ROCK活性。检测指标包括左心室重量、大小、功能和循环白细胞的ROCK活性,通过Western印迹检测肌球蛋白轻链磷酸酶1(MYPT1-p/t)的磷酸化水平。结果与正常血压组相比,高血压无左室肥厚组MYPT1-p/t显著增加4.5倍,高血压伴左室肥厚组增加9倍。高血压伴左室肥厚组MYPT1-p/t较高血压无左室肥厚组增加2倍。在有离心性左心室肥厚的高血压患者中,MYPT1-p/t的平均值比无离心性左心室肥厚的高血压患者高4倍。E/e比值为15(n=6)的高血压患者较E/e‘比值低的患者MYPT1-p/tratio升高26%(P=0.01)。结论高血压伴LVH患者SROCK活性高于高血压非LVH患者,偏心性LVH患者SROCK活性进一步升高。因此,在高血压中,ROCK的激活与病理性心脏重构有关,并可能作为左心室肥厚的标记物。
BACKGROUNDThere 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.METHODSWe 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).RESULTSCompared 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/tratio (by 26%) compared with patients with a lower E/e ' ratio (P = 0.01).CONCLUSIONSROCK 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.