Abstract 479: Smc Phenotype Switch Targeting Apoe is a Therapeutic Target in Popliteal Aneurysm

Abstract

Introduction: Popliteal artery aneurysm (PAA) is an individually highly fatal disease, causing ischemia and eventual major amputation, mainly in 50-70 year old males. It is the most frequent peripheral artery aneurysm and correct treatment is challenging for clinicians, since both open and endovascular repair have only modest success rates, depending on the clinical presentation. In comparison to other aneurysm entities, little is known about its specific pathogenesis. Material and Methods: 30 Human PAA and popliteal artery samples were analyzed by immunohistochemistry, mRNA and miRNA expression analysis and protein assays on the OLink platform in order to identify key features of the disease and crucial pathways involved. Furthermore, a novel murine model of PAA is characterized for future applications in basic research. Results: Vascular smooth muscle cells loose their contractile phenotype along with significant inflammatory and proteolytic changes in the vessel wall architecture. Extensive tissue remodeling with high cell turnover rates is a unique feature in comparison to AAA. This correlates with highly abundant expression of the apolipoproteins E and CI suggestive to have a pro-proliferative effect in peripheral vascular tissue. Additionally, array-based screening on gene and protein level revelaed the pentraxin-related protein 3 as a potential biomarker and soluble inducer of neutrophil homing. Other targets of interest in relation to ApoE were fatty acid binding protein 4 and Insulin growth facto binding protein 2. These findings are emphasized by a specific case of a solely mechanically induced PAA in a young male. Conclusion: Pathogenesis of PAA shows similar histologic features than AAA, yet differs in potential pathways involved. Increased cell turnover in the aneurysmal neck area suggests evaluation of alternative treatment strategies, targeting key processes in its pathogenesis.