title: Statins exert differential effects on angiotensin II-induced atherosclerosis, but no benefit for abdominal aortic aneurysms.
abstract: OBJECTIVE
  Statins reduce atherosclerosis, but it is controversial whether they suppress abdominal aortic aneurysm (AAA) expansion. We hypothesized that statins (rosuvastatin and atorvastatin) would attenuate angiotensin II (AngII)-induced atherosclerosis and AAA.
  
  
  RESULTS
  Sixty apoE-/- male mice fed a normal diet were administered with either rosuvastatin (10mg/kg/day) or atorvastatin (20mg/kg/day) through drinking water for 1 week prior to initiating 28-day AngII infusion (1000 ng/kg/min). Statins administration led to therapeutic serum concentrations of drugs. Administration of either rosuvastatin or atorvastatin exerted no significant effect on AngII-induced expansion of suprarenal diameter or area. However, atorvastatin significantly reduced AngII-augmented atherosclerotic lesion areas in intimas of both aortic arches and cross-sections of aortic roots (P<0.001). Atherosclerosis was attenuated independent of reductions in serum total cholesterol concentrations. Although serum MCP-1 and MIF concentrations were not changed by either statins, atorvastatin administration increased PPAR-α and -γ mRNA abundances and decreased NF-κB p50, p65, MCP-1 and TNF-α mRNA abundances in atherosclerotic lesions.
  
  
  CONCLUSIONS
  This study demonstrated both statins failed to suppress AngII-induced AAA. In contrast, atorvastatin reduced AngII-induced atherosclerosis associated with no change in serum inflammatory markers but a shift to upregulation of anti-inflammatory status in lesions.
authors.affiliation: Key Laboratory for Diagnosis and Treatment of Cardiovascular Disease of Zhejiang Province, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310009, PR China.
authors.forename: Jian-an
authors.initials: JA
authors.lastname: Wang
authors.forename: Wen-ai
authors.initials: WA
authors.lastname: Chen
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wang
authors.forename: Songzhao
authors.initials: S
authors.lastname: Zhang
authors.forename: Honghao
authors.initials: H
authors.lastname: Bi
authors.forename: Bo
authors.initials: B
authors.lastname: Hong
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Luo
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xie
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001011:Aorta / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D000069059:Atorvastatin; D001794:Blood Pressure; D005464:Fluorobenzenes / Q000494:pharmacology; D005786:Gene Expression Regulation; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000804:Angiotensin II; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin