title: Telmisartan prevents aneurysm progression in the rat by inhibiting proteolysis, apoptosis and inflammation.
abstract: OBJECTIVE
  We investigated the effects of treatment with the angiotensin II type 1 receptor antagonist, telmisartan, on abdominal aortic aneurysm formation in normotensive rats.
  
  
  METHODS
  Abdominal aortic aneurysm was induced by perfusion of an isolated aortic segment with elastase. Treatment with telmisattan (0.5 mg/kg per day) or hydralazine (15 mg/kg per day) was started after surgery and continued for 14 days. Sham-operated animals and vehicle-treated animals after aneurysm induction served as controls. Aortic diameter was measured using ultrasound before aneurysm induction and on days 7 and 14 after aneurysm induction.
  
  
  RESULTS
  On day 14, aortic diameter was increased two-fold in the vehicle-treated group compared to sham-operated animals (2.02 +/- 0.12 vs. 0.87 +/- 0.02 mm, P < 0.005, n = 8). Telmisartan treatment significantly reduced aneurysmal size (1.65 +/- 0.06 vs. 2.02 +/- 0.12 mm in vehicle, P < 0.05, n = 8), whereas treatment with hydralazine had no effect. Matrix metallopeptidase 3, cathepsin D, nuclear factor kappa B, tumour necrosis factor alpha, transforming growth factor-1 beta, as well as caspase 3, p53 and Fas ligand proteins, were significantly downregulated in aortic tissue under telmisartan compared to vehicle treatment. Serum monocyte chemoattractant protein 1 levels were also significantly decreased. Telmisartan and hydralazine reduced blood pressure to a similar extent within the observation period.
  
  
  CONCLUSIONS
  The angiotensin II type 1 receptor antagonist, telmisartan, prevents abdominal aortic aneurysm progression independently of blood pressure reduction by inhibiting proteolysis, apoptosis and inflammation in aortic tissue.
authors.affiliation: Center for Cardiovascular Research (CCR)/Institute of Pharmacology, Charité Universitätsmedizin Berlin, Berlin, Germany. elena.kaschina@charite.de
authors.forename: Elena
authors.initials: E
authors.lastname: Kaschina
authors.forename: Felix
authors.initials: F
authors.lastname: Schrader
authors.forename: Manuela
authors.initials: M
authors.lastname: Sommerfeld
authors.forename: Ulrich Rudolf
authors.initials: UR
authors.lastname: Kemnitz
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Grzesiak
authors.forename: Maxim
authors.initials: M
authors.lastname: Krikov
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011489:Protein Denaturation / Q000187:drug effects*; D051381:Rats; D011914:Rats, Inbred BN; D000077333:Telmisartan; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D006830:Hydralazine; D002402:Cathepsin D; D019278:Matrix Metalloproteinase 3; D000077333:Telmisartan