title: The therapeutic effect of rosuvastatin and propylthiouracil on ameliorating high-cholesterol diet-induced rabbit aortic atherosclerosis and stiffness.
abstract: 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.
  
  
  RESULTS
  Thirty-two New Zealand rabbits were equally divided into group 1 (sham-control), group 2 [high-cholesterol-diet (HCD) for 8weeks], group 3 [HCD-Rosu (20mg/kg/day administration after 4-week HFD for 4weeks)], 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).
  
  
  CONCLUSIONS
  Rosu-PTU therapy ameliorated aortic stiffness and inflammation/oxidative-stress, and improved endothelial-cell function after HCD challenge in rabbit.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Pao-Yuan
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.affiliation: Department of Plastic Surgery, University Hospital of South Manchester, Manchester, UK.
authors.forename: Christopher Glenn
authors.initials: CG
authors.lastname: Wallace
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuan-Hung
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Gour-Shenq
authors.initials: GS
authors.lastname: Kao
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Sheung-Fat
authors.initials: SF
authors.lastname: Ko
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan.
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shun-Cheng
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; Department of Nursing, Asia University, Taichung 41354, Taiwan.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
authors.affiliation: Department of Nursing, Asia University, Taichung 41354, Taiwan. Electronic address: m8951016@gmail.com.
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Shao
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D000068718:Rosuvastatin Calcium / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects* / Q000502:physiology
chemical_list: D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D011441:Propylthiouracil; D000068718:Rosuvastatin Calcium
keywords: Arterial stiffness; Arteriosclerosis; Hypercholesterolemia; Inflammation; Oxidative stress