Abstract 272: A Possible Role Of Apolipoprotein B In Degenerative Ascending Aortic Aneurysm Formation And Progression

Abstract

Background: Aortic valve regurgitation (AR) is associated with degenerative changes in the ascending aorta and the occurrence of ascending aortic aneurysm (AscAA). The molecular mechanism and initiating factors remain largely unknown, but leukocyte infiltration and inflammation are known characteristics. The aim of this study was to investigate the molecular signature of AR-associated degeneration and identify factors associated with degenerative AscAA formation. Material and Methods: Patients undergoing elective open-heart surgery for AscAA- and/or aortic valve surgery were included. Control samples were attained from organ donors. Histomorphology and protein expression/localization was assessed using immunohistochemistry, and gene expression in aortic intima-media was analyzed for totally n=16 non-dilated AR, n=19 non-dilated aortic stenosis (AS) and 36 dilated patients, as well as in n=6 controls. Results: Gene expression analysis showed that already prior to aortic dilatation, AR was associated with biological processes related to extracellular matrix turnover, as well as degenerative histological changes. In differential gene expression analysis of non-dilated vs dilated aortic tissue from AR-patients, genes with the greatest fold-change were PRPF40B, FMNL3, OLR1, MS4A7, MS4A14, of which OLR1 has a role in atherosclerosis and vascular inflammation. Apolipoprotein B 100 (ApoB) showed a different expression pattern between AR vs. AS patients with a high degree of medial infiltration in AR-patients. In AS-patients ApoB was almost exclusively localized to the endothelium. Further, the SRBI protein, a protein mediating LDL-transcytosis, was significantly increased in the endothelium of AR-patients compared with AS patients. Conclusions: The prevalence of AR-associated AscAA may involve an early infiltration of ApoB in the ascending aortic media, with possible down-stream implications for disease development. Further, this may explain the rarity of AscAA presenting with AS.