Abstract Th0003: Proinflammatory Changes in a Porcine Elastin Injury Model of Aneurysm

Introduction: We have previously reported a retrievable drug infusion stent graft (RDIS) which isolates anterior thoracic aortic wall from systemic circulation while maintaining distal perfusion and demonstrated an aneurysm model using three enzymes. This study explored a Porcine Elastin Injury Model (PEIM) to more specifically investigate the impact of elastin degradation alone. Methods: Anesthetized Yorkshire pigs underwent placement of an RDIS from a femoral access followed by elastase infusion and subsequent aspiration and RDIS retrieval. Animals were recovered and sacrificed at seven days (n=4). Tissue from untreated aorta and mid-aneurysm was analyzed with histology, multiplex analysis, and by flow cytometry. Primary cells were analyzed for cellular apoptosis and monocyte presence. Results: In the PEIM model, angiography revealed aneurysmal change averaging 30.6% by postoperative day seven (n=4, p=0.001) (Figure 1) . MOVAT pentachrome staining of explanted aorta revealed loss of cellularity and elastin, while multiplex analysis showed increased IL-18 expression on day seven (p=0.04) . By flow cytometry, primary digests of elastase injured aorta at day seven demonstrated a 15.4% increase in CD14+ cells compared to an untreated aorta control (n=2, p=0.01) (Figure 2). Conclusions: The PEIM model demonstrates aneurysm development with exposure to elastase alone. Elastase induces significant smooth muscle cell death and expression of inflammatory cytokines as well as monocyte infiltration when compared to normal aorta. Together, this data suggests elastin degradation causes cell death in smooth muscle cells and inflammatory infiltrate towards aneurysm formation.