Kajikawa Masato, Noma Kensuke, Nakashima Ayumu, Maruhashi Tatsuya, Iwamoto Yumiko, Matsumoto Takeshi, Iwamoto Akimichi, Oda Nozomu, Hidaka Takayuki, Kihara Yasuki, Aibara Yoshiki, Chayama Kazuaki, Sasaki Shota, Kato Masaya, Dote Keigo, Goto Chikara, Liao James K, Higashi Yukihito
From the Department of Cardiovascular Medicine, Graduate School of Biomedical Sciences (M.K., T. Maruhashi, Y.I., T. Matsumoto, A. I., N.O., T.H., Y.K.), Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (K.N., Y.H.), and Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Graduate School of Biomedical and Health Sciences (K.C.), Hiroshima University, Hiroshima, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan (K.N., A.N., Y.H.); Department of Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan (S.S., M.K., K.D.); Department of Physical Therapy, Hirohsima International University, Hiroshima, Japan (C.G.); and Section of Cardiology, University of Chicago Medical Center, IL (J.K.L.).
Hypertension. 2015 Oct;66(4):892-9. doi: 10.1161/HYPERTENSIONAHA.115.05587. Epub 2015 Aug 17.
Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender-matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95±0.55 versus 0.69±0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95±0.55 to 1.11±0.81 after 3 hours and reached a peak of 1.21±0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83±0.52 after 7 days, 0.78±0.42 after 14 days, and 0.72±0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98-11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome.
Rho相关激酶在多种细胞功能中发挥重要作用。尽管Rho相关激酶活性已被证明是普通人群未来心血管事件的独立预测因子，但急性冠状动脉综合征患者的Rho相关激酶活性尚无相关信息。我们通过蛋白质印迹分析评估了73例急性冠状动脉综合征患者和73例年龄及性别匹配的对照者的白细胞Rho相关激酶活性。急性冠状动脉综合征发作2小时内，患者的Rho相关激酶活性高于对照者（0.95±0.55对0.69±0.31；P<0.001）。3小时后，Rho相关激酶活性迅速从0.95±0.55升至1.11±0.81，1天后达到峰值1.21±0.76（分别为P=0.03和P=0.03），然后逐渐下降，7天后降至0.83±0.52，14天后降至0.78±0.42，6个月后降至0.72±0.30（分别为P=0.22、P=0.29和P=0.12）。在中位随访期50.8个月期间，发生了31例首次重大心血管事件（心血管原因死亡、心肌梗死、缺血性中风和冠状动脉血运重建）。在调整年龄、性别、心血管危险因素和他汀类药物的伴随治疗后，Rho相关激酶活性增加与首次重大心血管事件风险增加相关（风险比，4.56；95%置信区间，1.98 - 11.34；P<0.001）。这些发现表明，急性冠状动脉综合征后Rho相关激酶活性发生显著变化，且Rho相关激酶活性可能是预测日本急性冠状动脉综合征患者心血管事件的有用生物标志物。
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