Abstract:

Objective To examine the effects of fasudil, a specific Rho kinase inhibitor, on atherosclerotic plaque progression in apolipoprotein E-deficient (ApoE^-/-) mice, and explore the potential mechanisms. Methods After 12 weeks of fat-feeding, ApoE^-/- mice were orally administrated with fasudil for 12 weeks. Mice were randomly allocated into three groups: control group (tap water), low-dose fasudil group (30 mg•kg^-1•d^-1) and high-dose fasudil group (100 mg•kg^-1•d^-1) (n=10 in each group). At the end of the study, body weight, blood pressure and blood lipid were measured, and atherosclerosis of brachiocephalic arteries were determined by histological examinations. Production of superoxide anion and reactive oxygen species (ROS) were measured in the thoracic aorta of mice using chemiluminescence and histofluorescence techniques. Results Fasudil treatment had no effect on body weight, blood pressure and blood lipid concentrations of ApoE^-/- mice. The plaque area and intima-medial thickness of brachiocephalic artery were attenuated by 54% and 42%, respectively in high-dose fasudil group in comparison with control group (P<0.01 and P<0.05, respectively). Furthermore, fasudil treatment significantly reduced in situ ROS production of thoracic aorta (P<0.01). And the production of superoxide anion in the aortic wall was lower in high-dose fasudil group than in control group（P<0.05）. Conclusion Blocking Rho kinase may inhibit the progression of atherosclerotic plaques of brachiocephalic arteries in ApoE^-/- mice, and the effect may be independent of blood pressure and blood lipid changes, while probably be related with the anti-oxidative stress effect.

Key words: fasudil, atherosclerosis, oxidative stress, mice