Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Hypertens Res. 2010 Apr;33(4):354-9. doi: 10.1038/hr.2010.3. Epub 2010 Feb 5.
Rho-associated kinases (ROCKs) have been shown to be involved in the pathogenesis of atherosclerosis. Although smoking is associated with endothelial dysfunction and ROCK inhibitors improve endothelial function in smokers, it is not known whether ROCK activity is increased in smokers and whether this correlates with endothelial dysfunction. The purpose of this study was to evaluate the relationship between ROCK activity and endothelial function in smokers. We evaluated flow-mediated vasodilatation (FMD) using ultrasonography and ROCK activity in peripheral leukocytes using western blot analysis in 14 male smokers (28.1+/-3.9 years) and 15 healthy male non-smokers (28.3+/-3.6 years). ROCK activity was defined as the ratio of phospho-myosin-binding subunit (MBS) on myosin light-chain phosphatase to total MBS. FMD was significantly less in smokers than in non-smokers (4.7+/-3.1 vs. 9.0+/-3.8%, P=0.005). Nitroglycerine-induced vasodilation was similar in the two groups. ROCK activity was greater in smokers than in non-smokers (0.78+/-0.27 vs. 0.54+/-018, P=0.012). The expression of total MBS, ROCK1 and ROCK2 were similar in the two groups. ROCK activity correlated with systolic blood pressure (r=0.42, P=0.039). Multiple regression analysis revealed that smoking is an independent predictor of ROCK activity. There was a significant correlation between FMD and ROCK activity (r=-0.42, P=0.035). No other variable was correlated with FMD. These findings suggest that ROCK activity is enhanced by smoking and is a predictor of endothelial function.
Rho 相关激酶（ROCK）已被证明与动脉粥样硬化的发病机制有关。虽然吸烟与内皮功能障碍有关，ROCK 抑制剂可改善吸烟者的内皮功能，但尚不清楚吸烟者的 ROCK 活性是否增加，以及这是否与内皮功能障碍相关。本研究旨在评估吸烟者 ROCK 活性与内皮功能之间的关系。我们通过超声评估血流介导的血管舒张（FMD），并通过 Western blot 分析外周白细胞中的 ROCK 活性，纳入 14 名男性吸烟者（28.1+/-3.9 岁）和 15 名健康男性非吸烟者（28.3+/-3.6 岁）。ROCK 活性定义为肌球蛋白轻链磷酸酶上磷酸肌球蛋白结合亚基（MBS）与总 MBS 的比值。吸烟者的 FMD 明显低于非吸烟者（4.7+/-3.1 对 9.0+/-3.8%，P=0.005）。两组之间硝化甘油诱导的血管舒张相似。吸烟者的 ROCK 活性高于非吸烟者（0.78+/-0.27 对 0.54+/-018，P=0.012）。两组的总 MBS、ROCK1 和 ROCK2 的表达相似。ROCK 活性与收缩压相关（r=0.42，P=0.039）。多元回归分析显示，吸烟是 ROCK 活性的独立预测因子。FMD 与 ROCK 活性之间存在显著相关性（r=-0.42，P=0.035）。没有其他变量与 FMD 相关。这些发现表明，吸烟可增强 ROCK 活性，是内皮功能的预测因子。
