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 ± 7.4mm, 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.
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 ± 7.4mm, 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.