The Course of Circulating Small Extracellular Vesicles in Patients Undergoing Surgical Aortic Valve Replacement

Abstract

In the last years, increasing efforts have been devoted to investigating the role of small extracellular vesicles (sEVs) in cardiovascular diseases. These nano-sized particles (30-150 nm), secreted by different cell types, contain signalling molecules that enable participation in intercellular communication processes. In this study, we examined the course of circulating sEVs in patients undergoing surgical aortic valve replacement (SAVR) and correlated them with echocardiographic and standard blood parameters. Peripheral blood samples were collected from 135 patients undergoing SAVR preoperatively and at three follow-up points. Circulating sEVs were precipitated using Exoquick™ exosome isolation reagent and analyzed by nanoparticle tracking analysis (NTA). Our findings indicate that no more than 7 days after SAVR, there was a marked increase of circulating sEVs before returning to initial values after 3 months. Further, shear stress is not a trigger for the formation and release of circulating sEVs. Moreover, we pointed out a correlation between circulating sEVs and erythrocytes as well as LDH and creatinine levels in peripheral blood. Finally, all patients with a moderate prosthesis-patient mismatch as well as with an impaired left ventricular mass regression had lower levels of circulating sEVs 3 months after SAVR compared to their respective status before surgery. We conclude that in patients with aortic valve stenosis (AVS), sEVs may play an important part in mediating cell-cell communication and SAVR may have a crucial and lasting impact on their circulating levels. Besides, lower levels of sEVs portend to be associated with inferior recovery after major surgical interventions. The additional use of circulating sEVs beyond echocardiographic and laboratory parameters could have a prognostic value to estimate adverse outcomes in patients undergoing SAVR.

Figure 1

Flow diagram of the patient enrolment. SAVR: surgical aortic valve replacement; TAVI: transcatheter aortic valve implantation; PAD: peripheral artery disease; EF: ejection fraction.

Figure 2

Serum levels of circulating sEVs. Levels of sEVs of 135 patients receiving SAVR at four points (pre-OP, 24 h post-OP, 7 d post-OP, and 3 mo post-OP). Mean (blue line) ± SD; ^∗∗∗p < 0.001.

Figure 3

Correlation of pre-OP levels of sEVs with demographic parameters and BMI. (a) Gender-related differences of pre-OP levels of sEVs (mean ± SD) of 135 patients receiving SAVR. Correlation of pre-OP levels of sEVs with age (b) and BMI (c).

Figure 4

Correlation of sEVs with echocardiographic parameters in patients with AVS prior to SAVR. Linear regression of sEVs with aortic jet velocity (a), shear stress (b), effective orifice area (c), LV-mass (d), LV-mass index (e), and relative wall thickness (f) in patients before undergoing SAVR (n = 135).

Figure 5

Correlation of sEVs with laboratory parameters before SAVR. Linear regression of sEVs with thrombocytes (a), leucocytes (b), hemoglobin (c), hematocrit (d), lactate dehydrogenase (e), hsTnT (f), creatinine kinase (g), and creatinine (h) in patients before undergoing SAVR (n = 135).

Figure 6

Changes of circulating sEVs as predictor for PPM and LV-mass regression. Linear regression of ratios of sEVs (3 mo post-OP/pre-OP) with emerging PPM (a) and LV-mass regression (b) in patients undergoing SAVR (n = 135).