Downregulation of remodelling enzymatic activity induced by an angiotensin-converting enzyme inhibitor (perindopril) reduces the degeneration of experimental abdominal aortic aneurysms in a rat model

Abstract

Aims: Angiotensin-converting enzyme (ACE) inhibitors have proven their ability to affect vascular wall remodelling, in addition to their anti-hypertensive effects. The aim of this study was to assess the impact of perindopril on the development of abdominal aortic aneurysm (AAA) in a rat model, and its correlation to enzyme activities involved in vascular wall remodelling. Methods: The model of the decellularised aortic xenograft in Lewis rat was chosen. Rats were randomised to two groups: group P fed with 3 mg kg-1 of perindopril daily during 30 days, or control group C (n = 15 per group)). Rats were euthanised at 30 days for analysis. AAA growth and histological changes in the aortic wall were measured by histomorphometry. Proteolytic activities were measured by gelatin zymography of conditioned medium for activematrix metalloproteinase 9/pro-matrix metalloproteinase 9 (MMP9/pro-MMP9) and activeMMP2/pro-MMP2, and by quantitative immunofluorescence tissue for elastase and plasmin. Results: The mean maximal diameter of AAAs at 30 days was significantly lower in the treated group P compared with the control group C (2.5 ± 1.0 vs. 4.9 ± 2.1 mm; P < 0.01). The expansion rate of AAAs after 30 days was significantly reduced in group P compared with group C (36 ± 14% vs. 67 ± 23%; P < 0.01). Pro-MMP9 and MMP9 activities were significantly decreased in relative intensity (RI) in group P compared with group C (0.43 ± 0.64 RI vs. 1.02 ± 0.61 RI, P = 0.01; 0.18 ± 0.57 RI vs. 0.66 ± 1.19 RI, P = 0.004). The activation rate of MMP2 was also significantly lower in group P compared with group C (1.27 ± 0.42 vs. 1.67 ± 0.44; P = 0.002). Elastase and plasmin tissue activities were significantly lower in group P compared with group C, respectively (3.9 ± 3.3 vs. 5.8 ± 3.7 IF min-1 g-1,and 25.9 ± 23.9 vs. 49.1 ± 38.7 IF min -1 g-1; P < 0.05). Conclusion: After 30 days of treatment by perindopril, a significant decrease in aneurysmal degeneration of the decellularised aortic xenograft AAA model was observed. This phenomenon appears to be induced by a downregulation of enzymes involved in the aortic wall remodelling during aneurysmal degeneration. © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.