Abstract 438: Macrophages in a BAPN/AT2 Induced Model of Murine Aneurysm are Predominantly Lyve-1 and Tim-4 Negative

Abstract

Macrophages are key effector cells in aneurysm progression. Aneurysm macrophages may derive from monocyte recruitment and turnover of resident cells. We tested the hypothesis that aneurysm macrophages have a non-resident (lyve-1/tim-4 negative) phenotype. C57/Bl6 mice were administered beta-aminopropriononitrile (BAPN) and angiotensin-2 (AT2). At four weeks, whole aortas were excised, photomicrographed, and single cell suspensions created for immunophenotyping with flow cytometry. Results were compared to wild-type controls. BAPN/AT2 causes aortic dilatation (p<0.01) with maximal aneurysmal degeneration at the suprarenal aorta (wild-type control aortic diameter 0.93±0.03mm, n=8; BAPN/AT2 2.00±0.10mm, n=23; p<0.0001). BAPN/AT2 significantly increased aortic cd45+ myeloid-lymphoid cells and cd11b+ f4/80+ macrophages (p<0.02). Maximal aneurysm diameter correlated positively with aortic cell numbers of cd45+ myeloid-lymphoid cells (R=0.8168, p<0.001) and macrophages (R=0.5977, p=0.02). In wild-type, aortic macrophages are predominantly lyve-1 positive (67±3%, n=10). Whilst overall macrophage numbers are increased in aneurysm, the percentage of lyve-1 positive macrophages is significantly reduced (40±3%, n=18; p<0.001). The number of lyve-1 negative macrophages (R=0.6875, p=0.02), correlated with maximal suprarenal aortic diameter. In controls and aneurysm, lyve-1 positive, but not lyve-1 negative, macrophages are also tim-4 positive. In a BAPN/AT2 murine aneurysm model, aortic cd45+ myeloid-lymphoid cells and macrophages are increased and cell counts correlate with maximal aortic dilatation. Wild-type murine aortic macrophages are predominantly lyve-1/tim4 positive, with a significant relative increase in lyve-1/tim4 negative macrophages in aneurysm, suggesting lyve-1/tim-4 may indicate a resident macrophage phenotype.