Abstract 353: Phenotypic Switching Of Vascular Smooth Muscle Cells Is Regulated By ApoE And A Potential Therapeutic Target In Popliteal Aneurysms

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: 26 Human PAA and popliteal artery samples were analyzed by immunohistochemistry, mRNA and miRNA expression analysis and targeted proteomics (OLink platform) to identify key features of the disease and crucial pathways involved. Additionally, a primary cell culture of PAA specimen was established for in-vitro vascular smooth muscle cell (VSMC) modulation. Results: VSMCs lose their contractile phenotype along with significant inflammatory and proteolytic changes in the vessel wall architecture. Extensive tissue remodeling with high cell turnover rates (as indicated by Ki67+ cells) compared to non-diseased popliteal artery is a unique feature in comparison to AAA. This correlates with highly abundant co-expression of the apolipoproteins E and CI with Ki67 in VSMCs in double immune-fluorescent stains. Stimulation of VSMCs with external APOE or APOCI alters proliferation rates and significantly changes a subset of contractile markers proteins upon gene expression analysis. 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 key pathways involved. Increased cell turnover in the aneurysm neck area suggests evaluation of alternative treatment strategies, i.e., targeting key processes of pathogenesis such as angiogenesis and cell turnover.