title: Rosiglitazone reduces the development and rupture of experimental aortic aneurysms.
abstract: BACKGROUND
  Development and rupture of aortic aneurysms involve a combination of complex biological processes. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, has been shown to have a broad spectrum of effects in vivo. The hypothesis that rosiglitazone would reduce aneurysm expansion or rupture was tested in the angiotensin II (Ang II)-induced hypercholesterolemic mouse model.
  
  
  RESULTS
  Apolipoprotein E-deficient mice, 12 months of age, were allocated to 4 groups. Three groups were infused with Ang II (1 microg . min(-1) . kg(-1)), and the fourth was infused with saline. Rosiglitazone was given 1 week before infusion and 1 week after infusion. At day 28, aortic size was measured, and tissues were collected for analyses. Both pretreatment and posttreatment with rosiglitazone inhibited the occurrence of fatal rupture (11 of 30 versus 0 of 30 versus 0 of 15; P=0.0013) and reduced maximal dilatation of the aorta (4.6+/-0.13 versus 2.4+/-0.48 versus 2.15+/-0.46 mm2; P<0.0001). Blood glucose, total cholesterol, body weight, and atherosclerosis did not differ between groups. Pretreatment with rosiglitazone inhibited the Ang II-induced expression of angiotensin type 1a Ang II receptor while having no effect on the angiotensin type 2 Ang II receptor, in addition to reducing Ang II-induced expression of E-selectin, tumor necrosis factor-alpha, and interleukin-6.
  
  
  CONCLUSIONS
  Pretreatment or posttreatment with RGZ reduced aortic expansion and rupture in this mouse model. Reduction of lesions in animals pretreated with rosiglitazone is concomitant with decreased expression of inflammatory mediators. Further studies are needed to elucidate the precise mechanism.
authors.affiliation: Vascular Surgery Research Unit, Cranmer Terrace, Tooting, London, SW17 ORE, UK.
authors.forename: Alun
authors.initials: A
authors.lastname: Jones
authors.forename: Rajdeep
authors.initials: R
authors.lastname: Deb
authors.forename: Evelyn
authors.initials: E
authors.lastname: Torsney
authors.forename: Franklyn
authors.initials: F
authors.lastname: Howe
authors.forename: Mathew
authors.initials: M
authors.lastname: Dunkley
authors.forename: Yanosha
authors.initials: Y
authors.lastname: Gnaneswaran
authors.forename: David
authors.initials: D
authors.lastname: Gaze
authors.forename: Hosaam
authors.initials: H
authors.lastname: Nasr
authors.forename: Ian M
authors.initials: IM
authors.lastname: Loftus
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Thompson
authors.forename: Gillian W
authors.initials: GW
authors.lastname: Cockerill
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001019:Aortic Rupture / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D019040:E-Selectin / Q000097:blood; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000097:blood; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D019040:E-Selectin; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D047495:PPAR gamma; D011945:Receptors, Angiotensin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D000804:Angiotensin II; D002784:Cholesterol