Abstract 244: Targeted Deletion of Transcription Factor BATF Reduces Experimental Abdominal Aortic Aneurysm Formation and Progression

Abstract

Transcription factor BATF, a regulator of T cell IL-17-production and B cell immunoglobulin class switching, may be relevant in abdominal aortic aneurysm (AAA) disease pathogenesis. This study compared AAA formation following porcine pancreatic elastase (PPE) infusion in C57BL/6 and BATF-deficient mice. In wild-type mice, message for BATF and IL-17A was highly expressed in aneurysmal compared to control (PBS infusion) aortae. In BATF-deficient mice, aortic diameter enlargement following PPE infusion was almost completely suppressed, with preservation of medial elastin and smooth muscle cellularity, and attenuation of transmural aortic angiogenesis, leukocyte accumulation, and IL-17A-expressing CD4 T cells in peri-aortic lymph nodes and the spleen. AAA formation in response to PPE-infusion was rescued in BATF-deficient mice via either parenteral adminstration of IL-17A or wild-type murine leukocytes. In conclusion, BATF is essential for aneurysm formation following intraluminal aortic PPE infusion in C57BL/6 mice. BATF, IL-17A, or related T- and B-cell immunologic mediators may represent rational therapeutic targets for suppression of clinical AAA disease.