The therapeutic effect of rosuvastatin and propylthiouracil on ameliorating high-cholesterol diet-induced rabbit aortic atherosclerosis and stiffness

Background We tested the hypothesis that arteriosclerosis-augmented aortic pulse wave velocity (PWV) and -impaired vasorelaxation were attenuated by rosuvastatin (Rosu) and propylthiouracil (PTU) therapy. Methods and results Thirty-two New Zealand rabbits were equally divided into group 1 (sham-control), group 2 [high-cholesterol-diet (HCD) for 8 weeks], group 3 [HCD-Rosu (20 mg/kg/day administration after 4-week HFD for 4 weeks)], and group 4 [HCD-PTU (0.1% PTU in drinking water), the treatment course as group 3]. KCl-induced vasoconstriction of carotid artery (CA) was significantly higher in group 2 than in other groups (all p < 0.01), but showed no differences among groups 1, 3 and 4, whereas acetylcholine-induced vasorelaxation exhibited an opposite pattern of KCl-induced vasoconstriction among the four groups (p < 0.001). Basic nitric-oxide release from endothelial cells of CA was highest in group 1, lowest in group 2, but showed no difference between groups 3 and 4 (all p < 0.001). PWV value was highest in group 2, lowest in group 1, and significantly higher in group 4 than in group 3 (all p < 0.001). Serum levels of total-cholesterol, LDL and TG showed an identical pattern to PWV (all p < 0.001), whereas the levels of free T4, sugar, and body weight did not differ among the four groups (all p > 0.4). Aortic inflammatory biomarkers in cellular (CD68 +/IL-1β +/CD14 +) and protein (TNF-α/NF-κB/IL-1β/MMP-9/MCP-1/ICAM-1/PDGF) levels, and aortic oxidative-stress biomarkers in cellular (8-OHdG) and protein (NOX-1/NOX-2/oxidized protein) levels showed an identical pattern to PWV among the four groups (all p < 0.001). Conclusion Rosu-PTU therapy ameliorated aortic stiffness and inflammation/oxidative-stress, and improved endothelial-cell function after HCD challenge in rabbit.