title: Antiatherosclerotic effects of the novel angiotensin receptor antagonist Fimasartan on plaque progression and stability in a rabbit model: a double-blind placebo-controlled trial.
abstract: OBJECTIVE
  To evaluate the effect of the novel angiotensin receptor blocker Fimasartan on the development of atherosclerosis and plaque stabilization in an animal model.
  
  
  METHODS
  Twenty-four rabbits received an aortic balloon injury from 30 cm to a level just above the aortic valve to the iliac bifurcation using 3 Fr Fogarty catheters on third day of the experiment, followed by a 1% cholesterol diet for 8 weeks. The rabbits were randomized to receive placebo or 3 or 6 mg · kg⁻¹ · d⁻¹ Fimasartan. The study was double blinded. The rabbits started receiving their medications 2 days before the aortic balloon injury and treatment continued. Atherosclerosis burden was determined by calculating the intima-media ratio of the infrarenal portion of the aorta because the bulk of the atherosclerotic burden was limited to the infrarenal region. The frequency of plaque disruption with thrombosis and the proportions of the plaques that were occupied by macrophages, smooth muscle cells, and collagen were determined.
  
  
  RESULTS
  Relative to the placebo group, the Fimasartan-treated rabbits had less atherosclerosis [intima-media ratio (mean ± SEM) of 1.14 ± 0.21 vs. 1.51 ± 0.26, P = 0.005], fewer disrupted plaques with thrombi (3 of 16 vs. 5 of 8, P = 0.047), lower proportion of macrophages (17.5% ± 2.5% vs. 26% ± 3.5%, P = 0.03), higher proportion of smooth muscle cells (43.5% ± 8.3% vs. 11.9% ± 2.1%, P = 0.001), and higher proportion of collagen (34.3% ± 6.4% vs. 19.7% ± 2.1%, P = 0.02).
  
  
  CONCLUSIONS
  These results show that the newly developed angiotensin receptor blocker, Fimasartan, attenuated atherosclerosis progression and reduced macrophage accumulation in the rabbit aortic plaques.
authors.affiliation: Department of Cardiology, Asan Institute of Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Cheol Whan
authors.initials: CW
authors.lastname: Lee
authors.forename: Won-Jang
authors.initials: WJ
authors.lastname: Kim
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Ahn
authors.forename: Duk-Woo
authors.initials: DW
authors.lastname: Park
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Kang
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Lee
authors.forename: Young-Hak
authors.initials: YH
authors.lastname: Kim
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Jung
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Park
authors.forename: Seung-Jung
authors.initials: SJ
authors.lastname: Park
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001012:Aorta, Abdominal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D017539:Tunica Intima / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002317:Cardiovascular Agents; D011743:Pyrimidines; D013777:Tetrazoles; D003094:Collagen; C558933:fimasartan