title: Angiotensin II promotes aortic valve thickening independent of elevated blood pressure in apolipoprotein-E deficient mice.
abstract: BACKGROUND
  Valvular aortic stenosis (AS) is not an infrequent condition in the aged population. Activation of renin-angiotensin system (RAS) is presumed to be involved in the development of AS; however, direct evidence seems to be limited. We herein examined the effect of the administration of angiotensin II (Ang II) on the development of aortic valve thickening in apolipoprotein-E (ApoE)-deficient mice.
  
  
  RESULTS
  Male ApoE-deficient mice were divided into three groups: control (saline, n = 8), mice that were administered low-dose Ang II (500 ng/kg/min, n = 11), and those with high-dose Ang II (1000 ng/kg/min, n = 11) administration for 4 weeks. Administration of high-dose, but not low-dose, Ang II significantly induced aortic valve thickening. It was found that in the aortic valve leaflets of high-dose Ang II group, integrity of endothelial cells was impaired and the number of myofibroblasts was increased. These phenomena induced by high-dose Ang II were suppressed by Ang II type 1 receptor blocker olmesartan (n = 15), but not by the dilatator, hydralazine (n = 13). Olmesartan also suppressed dilatation of aortic diameter, although it did not significantly affect the plaque area, in the abdominal aorta in ApoE-deficient mice.
  
  
  CONCLUSIONS
  Administration of Ang II to genetically hyperlipidemic mice induced aortic valve thickening by a pressor-independent mechanism. Role of RAS activation in the development of AS in dyslipidemic patients should further be investigated.
authors.affiliation: Departments of Cardiology, Osaka Medical College, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujisaka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hoshiga
authors.forename: Junko
authors.initials: J
authors.lastname: Hotchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takeda
authors.forename: Denan
authors.initials: D
authors.lastname: Jin
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001021:Aortic Valve / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000209:etiology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology; D006973:Hypertension / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II