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. 2010 Apr;33(4):354-9.
doi: 10.1038/hr.2010.3. Epub 2010 Feb 5.

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

Takayuki Hidaka  1 , Takaki Hata, Junko Soga, Yuichi Fujii, Naomi Idei, Noritaka Fujimura, Yasuki Kihara, Kensuke Noma, James K Liao, Yukihito Higashi
Affiliations

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

Takayuki Hidaka et al. Hypertens Res. 2010 Apr.

Abstract

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.

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Conflict of interest statement

CONFLICT OF INTEREST

Dr James K Liao is a consultant for Asahi-Kasei Pharmaceutical.

Figures

Figure 1
Figure 1
Rho-associated kinase (ROCK) activity in smokers and non-smokers. (a) Western blot analysis for ROCK1, ROCK2, phospho-myosin-binding subunit (p-MBS), total-myosin-binding subunit (t-MBS) and β-tubulin. (b) ROCK activity (p-MBS/t-MBS) in smokers and non-smokers. (c) ROCK1 expression in smokers and non-smokers. (d) ROCK2 expression in smokers and non-smokers.
Figure 2
Figure 2
Relationship between Rho-associated kinase (ROCK) activity and systolic blood pressure.
Figure 3
Figure 3
Vascular function in smokers and non-smokers. (a) Flow-mediated vasodilation (FMD) in the smokers and non-smokers. (b) Nitroglycerine (NTG)-induced vasodilation in smokers and non-smokers.
Figure 4
Figure 4
Relationship between Rho-associated kinase (ROCK) activity and flow-mediated vasodilation (FMD).
See this image and copyright information in PMC

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