Circadian variation of Rho-kinase activity in circulating leukocytes of patients with vasospastic angina.
Circadian variation of Rho-kinase activity in circulating leukocytes of patients with vasospastic angina.
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DOI：
10.1253/circj.cj-13-1458
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发表时间：
2014
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通讯作者：
T. Nihei;J. Takahashi;R. Tsuburaya;Yoshitaka Ito;T. Shiroto;K. Hao;Yusuke Takagi;Y. Matsumoto;M. Nakayama;S. Miyata;Y. Sakata;K. Ito;H. Shimokawa
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文献类型：
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作者：
T. Nihei;J. Takahashi;R. Tsuburaya;Yoshitaka Ito;T. Shiroto;K. Hao;Yusuke Takagi;Y. Matsumoto;M. Nakayama;S. Miyata;Y. Sakata;K. Ito;H. Shimokawa
背景技术已知血管痉挛性心绞痛(VSA)表现出具有清晨高峰的昼夜节律变化。我们检查了循环白细胞中的 Rho 激酶活性（它是评估 VSA 疾病活动性的有用生物标志物）在 VSA 患者中是否表现出昼夜节律变化。方法和结果 在连续 31 名 VSA 患者（M/F 23/8，57±13 [SD] 岁）和 18 名非 VSA 患者（M/F 8/10，57±14 岁）中，我们在 6:00、12:00 和 21:00 测量了循环白细胞中的 Rho 激酶活性。我们还研究了激发试验期间 Rho 激酶活性与冠状血管舒缩反应之间的关系。 VSA患者的Rho激酶活性在6:00时显着高于非VSA患者（1.17±0.17 vs. 0.92±0.22，P<0.001），并表现出显着的昼夜变化，峰值出现在6:00（21:00为1.00±0.15，6:00为1.17±0.17， 1.12±0.22 12:00, P<0.001) VSA 患者，而在非 VSA 患者中没有发现这种变化。重要的是，VSA 患者痉挛激发试验中的 Rho 激酶活性与基础冠状动脉张力显着相关，基础冠状动脉张力由对冠状动脉内硝酸盐的血管舒张反应（r=0.40，P<0.05）和对乙酰胆碱的冠状血管收缩反应（r=0.44，P<0.05）定义。此外，通过动态心电图监测心率变异性评估，他们在6:00时的Rho激酶活性与夜间副交感神经活性呈正相关（r=0.48，P<0.05）。结论 Rho 激酶活性表现出明显的昼夜节律变化，与 VSA 患者冠状动脉血管舒缩反应和自主活动的改变相关。
BACKGROUND Vasospastic angina (VSA) is known to exhibit circadian variation with an early morning peak. We examined whether Rho-kinase activity in circulating leukocytes, which is a useful biomarker for disease activity assessment of VSA, exhibits circadian variation in patients with VSA. METHODS AND RESULTS In consecutive 31 VSA patients (M/F 23/8, 57±13 [SD] years) and 18 non-VSA patients (M/F 8/10, 57±14 years), we measured Rho-kinase activity in circulating leukocytes at 6:00, 12:00 and 21:00. We also examined the relationship between the Rho-kinase activity and coronary vasomotor responses during provocation test. Rho-kinase activity was significantly higher in VSA patients than in non-VSA patients at 6:00 (1.17±0.17 vs. 0.92±0.22, P<0.001), and showed a significant circadian variation with a peak at 6:00 (1.00±0.15 at 21:00, 1.17±0.17 at 6:00 and 1.12±0.22 at 12:00, P<0.001) in VSA patients, whereas no such variation was noted in non-VSA patients. Importantly, Rho-kinase activity at spasm provocation test was significantly correlated with basal coronary tone defined by vasodilating responses to intracoronary nitrate (r=0.40, P<0.05) and coronary vasoconstricting responses to acetylcholine (r=0.44, P<0.05) in VSA patients. Furthermore, their Rho-kinase activity at 6:00 was positively correlated with nocturnal parasympathetic activity as evaluated by heart rate variability in Holter monitoring (r=0.48, P<0.05). CONCLUSIONS Rho-kinase activity exhibits distinct circadian variation associated with alterations in coronary vasomotor responses and autonomic activity in VSA patients.