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Perindopril and Simvastatin Attenuate Dilation of the Descending Thoracic Aorta Via Down-Regulation of Interleukin-6 in an Experimental Model of CaCl2-Induced Aneurysm Formation

Abstract

Introduction: Some clinical studies aimed to discover potential pharmaceutical agents that could be used protectively against aneurysmal dilation of the aorta. Our study evaluates the role of perindopril and simvastatin in an experimental model of aortic aneurysm.

Materials and methods: Thirty-nine rabbits were allocated into 4 groups: control group, CaCl2 group, CaCl2+simvastatin group and CaCl2+perindopril group. All animals underwent to left posterolateral thoracotomy and normal or CaCl2 saline application on the wall of their descending thoracic aorta. The following parameters were evaluated: maximum vessel diameter, wall thickness, the presence of atherosclerosis, thickness of the atheromatous plaque and the expression of IL-6 and MMP-9 on the aortic wall.

Results: Aortas treated with CaCl2 presented apparent atherosclerosis in 75% of the cases as opposed to only 20% of the control aortas. Treatment with either simvastatin or perindopril significantly attenuated the effect of CaCl2 (4,145 ± 484 μm; p=0.039, and 4,209 ± 280 μm; p=0.05, respectively, compared with the CaCl2 group). Neither intensity nor extent of MMP-9 expression differed among groups. On the other hand, intensity of IL-6 expression was lower in both the simvastatin and perindopril-treated groups compared with the CaCl2 group (p=0.01). A significant positive correlation between aortic diameter and wall thickness was observed in the CaCl2 group (r=0.7; p=0.023), which was diminished in the simvastatin and perindopril groups (r=0.238; p>0.05, and r=0.05, p>0.05).

Conclusion: Our study shows the protective role of perindopril and simvastatin against aortic aneurysm formation and progression via down-regulation of local inflammation on the aortic wall.

Vasiliki Androutsopoulou, Despina N Perrea, Ilias P Doulamis, AspasiaTzani, Dimitrios C Iliopoulos, Nikolaos Kavantzas and Dimitrios C Angouras

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