Background-Development and rupture of aortic aneurysms involve a combination of complex biological processes.Rosiglitazone, a peroxisome proliferator-activated receptor-␥ 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. Methods and Results-Apolipoprotein E-deficient mice, 12 months of age, were allocated to 4 groups. Three groups were infused with Ang II (1 g · min Ϫ1 · kg Ϫ1 ), 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; Pϭ0.0013) and reduced maximal dilatation of the aorta (4.6Ϯ0.13 versus 2.4Ϯ0.48 versus 2.15Ϯ0.46 mm 2 ; PϽ0.0001). 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-␣, and interleukin-6. Key Words: aneurysm Ⅲ aneurysm, ruptured Ⅲ angiotensin Ⅲ inflammation Ⅲ polymerase chain reaction Ⅲ PPAR gamma R upture of an aortic aneurysm is the third-commonest cause of sudden death after myocardial infarction and stroke. Approximately 5% of men Ͼ60 years of age will develop an abdominal aortic aneurysm. Currently, the only treatment option for patients with aneurysms is surgical repair when the aneurysm expands past a critical point (usually a diameter threshold of 5.5 cm). Screening programs have begun to identify a large number of patients with small aortic aneurysms who would benefit from targeted pharmacotherapy to reduce aneurysm expansion and rupture. Conclusions-Pretreatment Clinical Perspective on p 3132Any potential pharmacological strategy to modulate the natural history of the aneurysmal process must be targeted to the biological process that mediates aneurysm expansion and rupture. Much of our understanding of the human pathogenesis of abdominal aortic aneurysm, obtained from analysis of aneurysmal biopsies during open surgery, is limited to analysis of the end-stage disease. Histological examination has identified that degeneration of the medial elastic fibers and compensatory deposition of collagens are accompanied by adventitial hypertrophy and infiltration of macrophages and T and B lymphocytes. Atherosclerosis and thrombus formation also are features of abdominal aortic aneurysm. [1][2][3][4] It is most likely that the dynamic remodeling process mediating the vascular changes observed in aneurysm development is the result of an initial inflammatory response. Involvement of inflammation as an instigating mechanism has been co...

Abdominal aortic aneurysm (AAA) rupture is associated with elevated levels of matrix metalloproteinase (MMP). Medial neovascularization is a known characteristic of established AAAs and involves proteolytic degradation of extracellular matrix by MMPs to facilitate endothelial cell proliferation and migration. This study evaluated the extent of neovascularization in abdominal aortic aneurysm rupture. Results indicated upregulation of proangiogenic cytokines and increased medial neovascularization at the aneurysm rupture edge compared with paired aneurysm anterior sac. Further investigations into the role of angiogenesis in aneurysm rupture may open novel therapeutic avenues to prevent aneurysm rupture.

To search for novel transcriptional pathways that are activated in abdominal aortic aneurysm rupture, cDNA microarrays were used to compare global mRNA expression at the aneurysm rupture edge to anterior sac, and selected results were confirmed using quantitative real-time-polymerase chain reaction (QRT-PCR). This study identified apoptosis, angiogenesis, and inflammation as potentially important participants during the process of aneurysm rupture.

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