Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease

Abstract

Popliteal artery aneurysm (PAA) is the most frequent peripheral aneurysm, primarily seen in male smokers with a prevalence below 1%. This exploratory study aims to shed light on cellular mechanisms involved in PAA progression. Sixteen human PAA and eight non-aneurysmatic popliteal artery samples, partially from the same patients, were analyzed by immunohistochemistry, fluorescence imaging, Affymetrix mRNA expression profiling, qPCR and OLink proteomics, and compared to atherosclerotic (n = 6) and abdominal aortic aneurysm (AAA) tissue (n = 19). Additionally, primary cell culture of PAA-derived vascular smooth muscle cells (VSMC) was established for modulation and growth analysis. Compared to non-aneurysmatic popliteal arteries, VSMCs lose the contractile phenotype and the cell proliferation rate increases significantly in PAA. Array analysis identified APOE higher expressed in PAA samples, co-localizing with VSMCs. APOE stimulation of primary human PAA VSMCs significantly reduced cell proliferation. Accordingly, contractile VSMC markers were significantly upregulated. A single case of osseous mechanically induced PAA with a non-diseased VSMC profile emphasizes these findings. Carefully concluded, PAA pathogenesis shows similar features to AAA, yet the mechanisms involved might differ. APOE is specifically higher expressed in PAA tissue and could be involved in VSMC phenotype rescue.

Current understanding of macrophages in intracranial aneurysm: relevant etiological manifestations, signaling modulation and therapeutic strategies

“…Recent single-cell transcriptome evidence demonstrated that ApoE + macrophages presented with overwhelming infiltration in some IA, and macrophage-derived ApoE potentially served as a biomarker to distinguish IA in molecular pathology ( 23 ). In vascular diseases, ApoE has been reported to reduced smooth muscle cells proliferation and be involved in phenotypic remodeling ( 24 ). As a lipid transport molecule, the ApoE relevant lipid efflux is a feature of peripheral vascular structural variations and aneurysm lesions ( 25 , 26 ).…”

Bypass Patency and Amputation-Free Survival after Popliteal Aneurysm Exclusion Significantly Depends on Patient Age and Medical Complications: A Detailed Dual-Center Analysis of 395 Consecutive Elective and Emergency Procedures

“…Compared with AAA, little is known about the specific pathogenesis of PAAs despite the popliteal artery being of a muscular rather than an elastic type [5,6]. However, the clinical presentation and symptoms differ.…”