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

• Published in: European journal of vascular and endovascular surgery 2011-04, Vol.41 (4), p.474-480
• Main Authors: Alsac, J.-M, Journe, C, Louedec, L, Dai, J, Julia, P, Fabiani, J.-N, Michel, J.-B
• Format: Article
• Language: English
• Subjects: Angiotensin I - blood; Angiotensin-converting enzyme inhibitor; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Aorta, Abdominal - drug effects; Aorta, Abdominal - enzymology; Aorta, Abdominal - pathology; Aorta, Abdominal - transplantation; Aortic Aneurysm, Abdominal - drug therapy; Aortic Aneurysm, Abdominal - enzymology; Aortic Aneurysm, Abdominal - etiology; Aortic Aneurysm, Abdominal - pathology; Aortic aneurysms; Aortic Rupture - enzymology; Aortic Rupture - pathology; Aortic Rupture - prevention & control; Blood Pressure - drug effects; Disease Models, Animal; Down-Regulation; Elastase; Enzymatic remodelling activity; Enzyme Precursors - metabolism; Fibrinolysin - metabolism; Gelatinases - metabolism; Guinea Pigs; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Metalloproteinase; Pancreatic Elastase - metabolism; Peptide Hydrolases - metabolism; Perindopril - pharmacology; Rats; Rats, Inbred Lew; Renin - blood; Surgery; Time Factors; Transplantation, Heterologous
• ISSN: 1078-5884; 1532-2165
• DOI: 10.1016/j.ejvs.2010.12.007

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