Abstract 147: Characterization of the Immune Response to Aortic Aneurysm in a Murine Model
Our understanding of vascular pathology relies on inducible animal models of disease that remain poorly described, and concern exists regarding indirect effects of the inducing agents. We sought to perform a detailed characterization of the immune response to a commonly used murine aneurysm model.
Aneurysms were generated in 10 adult C57/Bl6 mice using 2 weeks of oral beta-amino propriono-nitrile (BAPN) administration and 4 weeks of angiotensin-2 (AT2) delivered via osmotic pump. FACS analysis was used to characterize progenitor and hematopoietic cell lines in bone marrow, blood and aorta. 3 mice died of aortic rupture between days 8 and 9. The remaining 7 were compared to age-matched controls.
BAPN/AT2 treatment caused aortic dilatation at all aortic regions from the root to the descending thoracic aorta (P<0.01). The suprarenal aorta was aneurysmal in all BAPN/AT2 mice with a maximum diameter of 1.86±0.1mm compared to controls 0.98±0.03mm (P<0.001). In the blood, total cells counts at day 2, 16 and 28 were increased (P<0.001). CD45-2 and B-cell counts were significantly increased in the BAPN/AT2 mice compared to controls (P<0.001). The aorta of BAPN/AT2 mice had significantly increased macrophage counts (P<0.001) with no difference in monocytes, neutrophils, T or B cell counts. Aortic tissue macrophages were predominantly G0 G1 (97±1%) phase. The bone marrow CD45-2 compartment was similar in aneurysmal BAPN/AT2 and control mice but Ly6C lo-inter monocytes were increased in BAPN/AT2 mice. Marrow CD117+/lin- hematopoietic progenitor and stem cells (P=0.4), and differential counts of CD117+/Sca1+ hematopoietic stem cells and CD117+/Sca1- progenitor cells were similar in control and BAPN/AT2 treated mice.
BAPN/AT2 induces aortic disease with aneurysmal degeneration of the suprarenal aorta. We observed a significant decrease in aortic macrophage proliferation suggestive of a mechanism of expansion independent of local macrophage proliferation. We did not observe a significant change in the bone marrow stem or progenitor cell compartment suggesting aortic injury is driving inflammation rather than direct stimulus of the marrow compartment by BAPN/AT2.
Author Disclosures: J.S. Byrne: None. R. Besla: None. S. Ensan: None. A. Li: None. N. Degousee: None. M. Ouzounian: None. T. Lindsay: None. C. Robbins: None.
- © 2015 by American Heart Association, Inc.