The Course of Blood Cell-Derived Extracellular Vesicles in Patients Undergoing Surgical Aortic Valve Replacement

Objectives: Research on biology, function, and potential application of extracellular vesicles (EVs) increased exponentially in the last decade. These submicron vesicles (0.1–3 μm), generated by various cell types are known to facilitate intercellular communication in diverse cellular processes. In patients with aortic valve stenosis (AVS), increased shear stress triggers the release of EVs, which then contribute to the progression of AVS.

Methods: Patients undergoing surgical aortic valve replacement (SAVR) were enrolled (n = 118, 70 males, 72.4 ± 7.7 years) over a 12 month period. Blood cell–derived microparticles (MPs, 0.5–1 µm) and apoptotic bodies (ApoBDs, 1–2 µm) were analyzed preoperatively (pre-OP) and at three follow-up points (24 hours postoperatively [post-OP], 7 days post-OP and 3 months post-OP) by flow cytometry. Levels were determined for MPs and ApoBDs derived from platelets (CD41+), erythrocytes (CD235a+), leucocytes (CD45+), lymphocytes (CD3+), granulocytes (CD66b+) and monocytes (CD11b+). Plasma levels of IL-1β, IL-6, and RANTES were measured with ELISA.

Result: Total levels of both MPs and ApoBDs decrease 24 hours post-OP (p < 0.001), with a marked recovery thereafter at 7 days post-OP (p < 0.001) before ascending above pre-OP values 3 months post-OP (p < 0.05). The levels of MPs are distinctly higher compared with ApoBD levels at all time-points (p < 0.001). Levels of CD41+ MPs increase 24 hours post-OP (p < 0.001) and decrease 3 months post-OP compared with pre-OP levels (p < 0.001). Levels of CD41+ ApoBDs increase 7 days post-OP (p < 0.01) before descending under their pre-OP values 3 months post-OP (p < 0.001). While Levels of CD235a+ MPs decrease at the 3 months of follow-up (p < 0.05), levels of ApoBDs decline 24 hours post-OP (p < 0.001), ascend at 7 days post-OP (p < 0.05) before decreasing 3 months-post-OP compared with pre-OP levels (p < 0.001). Levels of CD45+, CD3+, CD66b+, and CD11b+ MPs and ApoBDs increase 7 days post-OP (p < 0.01) before descending under their pre-OP values 3 months post-OP (p < 0.05). IL-6, IL-1β, and RANTES increase after SAVR but do not correlate with leucocyte-derived EVs.

Conclusion: Blood cell-derived EVs are clearly altered after SAVR. The increased levels 7 days after SAVR, in particular ApoBDs, may be an indicator of the general response and the physical recovery. These data suggest that circulating EVs are not generated as a response to pathological conditions of AVS, but rather provide a permanent communication system, which is quickly regenerated after major surgical interventions.

Publication History

Article published online:
19 February 2021