Evaluation of Circulating Microparticles and Exosomes as Potential Biomarkers for Left Ventricular Hypertrophy in the Course of Aortic Valve Replacement
22 January 2018 (online)
Objectives: Cell-derived microparticles (MPs) have emerged as potential biomarkers in different diseases. Increased plasma levels of endothelial or platelet derived MPs have been described for cardiovascular pathologies including severe aortic stenosis (AS). In this study we investigated the course of circulating MPs in patients undergoing conventional aortic valve replacement (AVR) and their relation to left ventricular (LV) hypertrophy.
Methods: Patients undergoing AVR and fulfilling further study criteria were enrolled (n = 78, 40 males, 72.4 ± 7.7 years) from 07/15–08/16. Peripheral blood was analyzed at 3 time points (t1=pre-operative [pre-OP], t2=7 days post-operative [pOP], t3=3 months pOP). MPs were isolated from EDTA-plasma by centrifugation and quantified by flow cytometry. MP levels were determined for MPs derived from platelets (CD41+; PMPs), erythrocytes (CD235a+; ERMPs) and endothelial cells (CD31+; EMPs). Exosomes (30–150 nm) were isolated with Exoquick and analyzed by particle tracking analysis (Zeta View).
Results: The number of exosomes did not change between t1 (1.09*109/mL) and t3 (1.07*109/mL), while MPs, separated in two groups (G1:1–2µm; G2:0.5–1µm) increased from t1 (G1:5.11*105/µL; G2:9.52*105/µL) to t3 (G1:6.39*105/µL, p < 0.01; G2:1.07*106/µL, p = 0.12). After sorting for their cellular origin, PMPs increased in both groups from t1 to t2 (p < 0.05) and decreased from t2 to t3 (p < 0.01). ERMPs and EMPs decreased in both groups from t1 to t3 (p < 0.05). LV-mass-index decreased from t1 to t3 in male (p < 0.05) and female (p < 0.001) patients. A correlation between the ratio (t3/t1) of MPs (p < 0.001) as well as exosomes (p < 0.01) and the LV-mass-index at t1 was detected for male patients. Higher LV-mass loss (t1-t3) correlated with an increase of MPs (G1 and G2; p < 0.001) and exosomes (p < 0.05) from t1 to t3 in patients with severe pre-OP stenosis (mean pressure gradient >50 mm Hg). No correlation could be detected between PMPs, ERMPs or EMPs with the LV-mass-index.
Conclusion: This clinical study observed a correlation between the ratio of MPs (t3/t1) and pre-OP LV-hypertrophy index in male patients with AS. The ratio of exosomes and MPs correlated with LV-mass loss. Our results suggest a promising supplement for established clinical parameters for monitoring LV-hypertrophy changes in patients undergoing AVR by analyses of peripheral blood. Further studies should focus on the differential behavior of MPs in male and female patients with AS.
No conflict of interest has been declared by the author(s).