Inadequate reinforcement of transmedial disruptions at branch points subtends aortic aneurysm formation in apolipoprotein-E-deficient mice

AbstractIntroduction on of angiotensin-II (Ang-II) in apolipoprotein-E-deficient mice (Apo-E-/-) results in suprarenal abdominal aortic aneurysm (AAA) in 30–85% of cases. This study identifies the apparent mechanism by which some animals do, but others do not, develop AAA in this model. s po-E-/- mice were infused with Ang-II (n=21) or saline (n=6) and sacrificed at 4 weeks. Aortas were excised, embedded in paraffin, sectioned (250 μm intervals), and stained. Sites of transmedial disruption (TMD) were identified and characterized, and their relationship to the 4 major aortic side branches (celiac, superior mesenteric, and renals) were determined. s equency of TMDs in Ang-II-infused mice that formed AAA (n=9) was similar to those that did not (n=12) (AAA vs. no-AAA: 25 of 36[69%] vs. 28 of 48[58%] branches, P=.3 by chi-square). All TMDs were at branch points. However, in animals with AAA, the mean maximum length of the TMDs was significantly larger (1.94±1.6 vs. 0.65±0.5mm, P=.007 by Mann Whitney U test), the #mac-2+ macrophages per 0.01mm2 of defect area was greater (32±10 vs. 19±11, P<.02 by Kruskal–Wallis with Conover–Inman post hoc), the % area of attempted repair occupied by collagen was less (17±13% vs. 44±15%, P=.0009 by Mann Whitney U test), and the density of collagen per unit length of media missing was also markedly less (0.13±0.2 vs. 1.14±1.0, P=.0001 by Mann Whitney U test). sions rcement of transmedial defects at branch points by wall matrix is a key intrinsic player in limiting AAA formation in the Ang-II-infused, Apo E-/- mouse and a potentially important mechanism-based therapeutic target for management of small, slowly progressing aneurysms.