Abstract Background Ascending aortic aneurysm (AscAA) involves progressive dilation of the ascending aorta, which can lead to fatal rupture or dissection. The underlying pathogenesis remains poorly understood, limiting treatment and prediction options. Degenerative AscAA frequently coexists with aortic regurgitation (AR), but rarely with aortic stenosis (AS). and our previous findings have demonstrated that endothelial mesenchymal activation precedes dilation in AR-patients. Extracellular vesicles (EVs) have emerged as important contributors to aneurysm development by promoting endothelial dysfunction through direct interaction or uptake. Purpose To study circulating (plasma) EVs from patients with AR and AS and investigate their impact on endothelial integrity and function. We hypothesize that AR-derived EVs carry different cargo/proteins than EVs from AS patients, causing endothelial dysfunction and vascular remodelling. Methods ASAP/DAVAACA patients undergoing isolated valve replacement for AR or AS were included. Patients were matched for age, sex, diabetes, hypertension, smoking, and absence of coronary disease. Plasma-derived EVs were isolated and used in cell-based assays assessing e.g., endothelial reactive oxygen species (ROS) and nitric oxide (NO) production. ROS was also evaluated in aortic specimen using IHC. Vascular function was determined by wire myograph. Results Circulating EVs from AR-patients induced higher endothelial ROS than AS-patients, but increased NO was found in both groups. Non-dilated aortas from AR-patients showed higher ROS production than AS-patients, accompanied by increased 3-nitrotyrosine residues in the intima. Besides, AR-EVs upregulated genes associated with endothelial mesenchymal activation in comparison with AS-EVs and modulated others related to vascular integrity and LDL transport. Moreover, circulating EVs from AS and AR-patients modulate vascular function. Conclusions Circulating EVs from AR patients exert vascular function impairment and endothelial dysfunction in human aortic endothelial cells, possibly contributing to the increased oxidative stress seen in the aorta of these patients.Figure 1.For image description, please refer to the figure legend and surrounding text. Figure 2.For image description, please refer to the figure legend and surrounding text.
Goya et al. (Fri,) studied this question.