Abstract 665: Conditional Deficiency of Myeloid Cell Hif-2α Activity Promotes Aneurysmal Aortic Degeneration

Abstract

Abdominal aortic aneurysm (AAA) is a chronic degenerative disease mediated by myeloid cells, particularly macrophages. The transcription factor hypoxia inducible factor (HIF)-2α is a potent modulator of macrophage activation/ polarization. A potential role for HIF-2α in aneurysm pathogenesis has yet to be demonstrated. To consider this role, we created experimental AAA in conditional, myeloid cell-specific HIF-2α deficient mice (CKO) by intra-aortic infusion of porcine pancreatic elastase (PPE). Following PPE infusion, serial ultrasound imaging demonstrated progressively larger aneurysms in HIF-2α CKO mice, characterized by increased aortic medial elastin fragmentation and smooth muscle cell depletion, compared to WT controls. Aortic accumulation of CD68+ macrophages and CD4+ T cells, as well as aortic mural CD31+ neovessel formation were also augmented in HIF-2α CKO mice. These observations suggest that myeloid cell-derived HIF-2α activity may limit aneurysm pathogenesis and influence progression of AAA disease.