Aortic Length Changes During Abdominal Aortic Aneurysm Formation, Expansion and Stabilisation in a Rat Model

Abstract

Background Determinants of extracellular matrix (ECM) destruction/reconstruction balance influencing abdominal aortic aneurysm (AAA) diameter may impact length. Objective Document aortic lengthening, its correlation to diameter, and determine how treatments that impact diameter also affect length. Methods Three hundred and fifty-five diameter and length measurements were performed in 308 rats during AAA formation, expansion and stabilisation in guinea pig aortas xenografted in rats. Impact of modulation of ECM destructive/reconstructive balance by endovascular Vascular Smooth Muscle Cell (VSMCs) seeding, TIMP-1, PAI-1 and TGF-beta1 overexpression on length has been assessed. Results Length increased in correlation with diameter during formation (correlation coefficient (cc): 0.584, P < 0.0001) and expansion (cc: 0.352, P = 0.0055) of AAAs. Overexpression of TIMP-1 and PAI-1 decreased lengthening ( P = 0.02 and 0.014, respectively) demonstrating that elongation is driven by matrix metalloproteinases and their activation by the plasmin pathway. Overexpression of TGF-beta1 controlled length in formed AAAs (17.3 ± 9.6 vs. 5.9 ± 7.4 mm, P = 0.022), but not VSMC seeding, although both therapies efficiently prevented further diameter increase. Length and diameter correlation was lost after biotherapies. Conclusion Length increases in correlation with diameter during AAA formation and expansion, as a consequence of ECM injury driven by MMPs activated by the plasmin pathway. Correlation between length and diameter increases is not universally preserved.