Increased leukocyte rho kinase (ROCK) activity and endothelial dysfunction in cigarette smokers

被引:29
作者
Hidaka, Takayuki [2 ]
Hata, Takaki [2 ]
Soga, Junko [2 ]
Fujii, Yuichi [2 ]
Idei, Naomi [2 ]
Fujimura, Noritaka [2 ]
Kihara, Yasuki [2 ]
Noma, Kensuke
Liao, James K. [3 ,4 ]
Higashi, Yukihito [1 ]
机构
[1] Hiroshima Univ, Grad Sch Biomed Sci, Dept Cardiovasc Physiol & Med, Mimami Ku, Hiroshima 7348551, Japan
[2] Hiroshima Univ, Grad Sch Biomed Sci, Dept Cardiovasc Med, Hiroshima 7348551, Japan
[3] Brigham & Womens Hosp, Vasc Med Res Unit, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA USA
基金
美国国家卫生研究院;
关键词
endothelial function; Rho-associated kinase; smoker; PROTEIN-KINASE; SMOOTH-MUSCLE; SMOKING; ATHEROSCLEROSIS; DISEASE; CELLS; MICE; SENSITIZATION; HYPERTENSION; PATHOGENESIS;
D O I
10.1038/hr.2010.3
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 phosphomyosin-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. Hypertension Research (2010) 33, 354-359; doi:10.1038/hr.2010.3; published online 5 February 2010
引用
收藏
页码:354 / 359
页数:6
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