Increased Rho kinase activity in congestive heart failure
Increased Rho kinase activity in congestive heart failure
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DOI：
10.1093/eurjhf/hfs068
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发表时间：
2012-09-01
影响因子：
18.2
通讯作者：
Yu, Cheuk-Man
中科院分区：
文献类型：
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作者：
Dong, Ming;Liao, James K.;Yu, Cheuk-Man
Rho激酶(ROCK)是小G蛋白RhoA的最具特征的效应器，在充血性心力衰竭(CHF)动物模型中发挥增强血管收缩的作用。这项研究考察了CHF患者(n 178例)、疾病对照组(n 31例)和正常受试者(n 30例)的ROCK活性是否增加，以及它与CHF患者预后的关系。通过外周血白细胞肌球蛋白结合亚单位的磷酸化来测量基线ROCK活性。术后随访14.4~7.2个月(0.526个月)，直至发生心源性死亡。CHF组ROCK活性(2.93±0.87)显著高于疾病对照组(2.06±0.38，P<0.001)和正常对照组(1.57±0.43，P<0.001)。CHF组ROCK1、ROCK2蛋白水平及RhoA活性均显著高于疾病对照组和正常对照组(均P<0.05)。静息时呼吸困难(0.338，P 0.001)、低左室射血分数(0.277，P 0.001)和高肌酐(0.202，P 0.006)是CHF患者基础ROCK活动的独立预测因素。随访2年内死亡45例(25.3%)。联合检测ROCK活性和N-末端脑利钠肽原(NT-proBNP)预测远期死亡率较单独检测NT-proBNP增加11.62(对数值2)5.16(P<0.05)，ROCK活性在CHF时升高，可能与CHF的死亡率有关。岩石活动可能是CHF风险分层的补充生物标志物。
Rho kinases (ROCKs) are the best characterized effectors of the small G-protein RhoA, and play a role in enhanced vasoconstriction in animal models of congestive heart failure (CHF). This study examined if ROCK activity is increased in CHF and how it is associated with the outcome in CHF.Patients admitted with CHF (n 178), disease controls (n 31), and normal subjects (n 30) were studied. Baseline ROCK activity was measured by phosphorylation of themyosin-binding subunit in peripheral leucocytes. The patients were followed up for 14.4 7.2 months (range 0.526 months) or until the occurrence of cardiac death. The ROCK activity in CHF patients (2.93 0.87) was significantly higher than that of the disease control (2.06 0.38, P 0.001) and normal control (1.57 0.43, P 0.001) groups. Similarly, protein levels of ROCK1 and ROCK2 as well as the activity of RhoA in CHF were significantly higher than in disease controls and normal controls (all P 0.05). Dyspnoea at rest ( 0.338, P 0.001), low left ventricular ejection fraction ( 0.277, P 0.001), and high creatinine ( 0.202, P 0.006) were independent predictors of the baseline ROCK activity in CHF. Forty-five patients died within 2 years follow-up (25.3). Combining ROCK activity and N-terminal pro brain natriuretic peptide (NT-proBNP) had an incremental value (log rank (2) 11.62) in predicting long-term mortality when compared with only NT-proBNP (log rank (2) 5.16, P 0.05).ROCK activity is increased in CHF and it might be associated with the mortality in CHF. ROCK activity might be a complementary biomarker to CHF risk stratification.