Abstract We0014: Endothelial Mesenchymal Activation And Lipoprotein Infiltration In Patients With Regurgitant Aortic Valves – Part Of The Natural History Of Degenerative Ascending Aortic Aneurysm

Aims: An abnormal accumulation of immune cells has been described in ascending aortic aneurysm, but the factor driving its initiation remains elusive. Ascending aortic dilatation often occurs alongside aortic regurgitation but rarely with aortic stenosis. We sought to investigate ascending aortic aneurysm initiation by assessing the relation between aortic regurgitation and vascular inflammation. Material and Results: In this prospective cohort study, patients undergoing elective surgery open-heart surgery were included. Aortic specimens from organ donors were obtained through the University of Miami Tissue Bank. Spatial transcriptomics measured gene expression in non-dilated aortic endothelium, intima and subintima. Immunohistochemistry determined protein expression. Aortic dimensions were recorded pre-operatively and ten years after surgery using echocardiography. We show a mesenchymal activation of endothelial cells in the non-dilated ascending aorta of patients with aortic valve regurgitation, accompanied by intimal infiltration, retention and oxidation of apolipoprotein B-containing lipoproteins. Intimal upregulation of core proteins of lipoprotein-binding proteoglycans and the Oxidized Low Density Lipoprotein Receptor 1 ( OLR1 ) by infiltrating macrophages, associated with progressive inflammation and matrix degeneration. None of the above was observed in patients with aortic stenosis. Notably, surgical replacement of regurgitant valves, but not stenotic valves, mitigated 10-year aortic growth. Conclusions: Our results highlight a distinct pathological role of aortic valve regurgitation in ascending aortic aneurysm formation by promoting mesenchymal activation of endothelial cells and lipoprotein-related immune cell infiltration and inflammation. We also provide new insights into the long-term impact of surgical aortic valve replacement on ascending aortic growth.