title: Efficacy and mechanism of angiotensin II receptor blocker treatment in experimental abdominal aortic aneurysms.
abstract: BACKGROUND
  Despite the importance of the renin-angiotensin (Ang) system in abdominal aortic aneurysm (AAA) pathogenesis, strategies targeting this system to prevent clinical aneurysm progression remain controversial and unproven. We compared the relative efficacy of two Ang II type 1 receptor blockers, telmisartan and irbesartan, in limiting experimental AAAs in distinct mouse models of aneurysm disease.
  
  
  RESULTS
  AAAs were induced using either 1) Ang II subcutaneous infusion (1000 ng/kg/min) for 28 days in male ApoE(-/-) mice, or 2) transient intra-aortic porcine pancreatic elastase infusion in male C57BL/6 mice. One week prior to AAA creation, mice started to daily receive irbesartan (50 mg/kg), telmisartan (10 mg/kg), fluvastatin (40 mg/kg), bosentan (100 mg/kg), doxycycline (100 mg/kg) or vehicle alone. Efficacy was determined via serial in vivo aortic diameter measurements, histopathology and gene expression analysis at sacrifice. Aortic aneurysms developed in 67% of Ang II-infused ApoE(-/-) mice fed with standard chow and water alone (n = 15), and 40% died of rupture. Strikingly, no telmisartan-treated mouse developed an AAA (n = 14). Both telmisartan and irbesartan limited aneurysm enlargement, medial elastolysis, smooth muscle attenuation, macrophage infiltration, adventitial neocapillary formation, and the expression of proteinases and proinflammatory mediators. Doxycycline, fluvastatin and bosentan did not influence aneurysm progression. Telmisartan was also highly effective in intra-aortic porcine pancreatic elastase infusion-induced AAAs, a second AAA model that did not require exogenous Ang II infusion.
  
  
  CONCLUSIONS
  Telmisartan suppresses experimental aneurysms in a model-independent manner and may prove valuable in limiting clinical disease progression.
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iida
authors.forename: Baohui
authors.initials: B
authors.lastname: Xu
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Schultz
authors.forename: Vinca
authors.initials: V
authors.lastname: Chow
authors.forename: Julie J
authors.initials: JJ
authors.lastname: White
authors.forename: Shola
authors.initials: S
authors.lastname: Sulaimon
authors.forename: Ayala
authors.initials: A
authors.lastname: Hezi-Yamit
authors.forename: Susan Rea
authors.initials: SR
authors.lastname: Peterson
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Dalman
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000517:prevention & control; D001057:Apolipoproteins E / Q000235:genetics; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000077300:Bosentan; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use; D000077340:Fluvastatin; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D000077405:Irbesartan; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D000077333:Telmisartan; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001057:Apolipoproteins E; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D013449:Sulfonamides; D013777:Tetrazoles; D000077340:Fluvastatin; D000077405:Irbesartan; D004318:Doxycycline; D000077300:Bosentan; D000077333:Telmisartan