Rosiglitazone Reduces the Development and Rupture of Experimental Aortic Aneurysms

Article

关键词: ACTIVATED RECEPTOR-GAMMA;    ANGIOTENSIN-II;    PPAR-GAMMA;    GENE-EXPRESSION;    BLOOD-PRESSURE;    ATHEROSCLEROTIC LESIONS;    ENDOTHELIAL FUNCTION;    INFLAMMATION;    INHIBITION;    PROTECTS;   

DOI  :  10.1161/CIRCULATIONAHA.109.852467

来源: SCIE

【 摘 要 】

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. Methods and Results-Apolipoprotein E-deficient mice, 12 months of age, were allocated to 4 groups. Three groups were infused with Ang II (1 mu g . 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 mm(2); 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. (Circulation. 2009; 119: 3125-3132.)

【 授权许可】

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