Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms

• Published in: Circulation (New York, N.Y.) N.Y.), 2009-06, Vol.119 (24), p.3125-3132
• Main Authors: JONES, Alun, DEB, Rajdeep, COCKERILL, Gillian W, TORSNEY, Evelyn, HOWE, Franklyn, DUNKLEY, Mathew, GNANESWARAN, Yanosha, GAZE, David, NASR, Hosaam, LOFTUS, Ian M, THOMPSON, Mathew M
• Format: Article
• Language: English
• Subjects: Angiotensin II - adverse effects; Angiotensin II - pharmacology; Animals; Aortic Aneurysm, Abdominal - blood; Aortic Aneurysm, Abdominal - chemically induced; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - pathology; Aortic Aneurysm, Abdominal - prevention & control; Aortic Rupture - blood; Aortic Rupture - chemically induced; Aortic Rupture - genetics; Aortic Rupture - prevention & control; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - analysis; Body Weight - drug effects; Cardiology. Vascular system; Cholesterol - blood; Disease Models, Animal; Diseases of the aorta; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; E-Selectin - blood; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - chemically induced; Hypercholesterolemia - genetics; Hypercholesterolemia - pathology; Hypercholesterolemia - prevention & control; Hypoglycemic Agents - pharmacology; Interleukin-6 - blood; Medical sciences; Mice; Mice, Knockout; PPAR gamma - agonists; PPAR gamma - genetics; PPAR gamma - metabolism; Receptors, Angiotensin - blood; Thiazolidinediones - pharmacology; Tumor Necrosis Factor-alpha - blood
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.109.852467

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. 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