Abstract
This study sought to identify different subpopulations of extracellular vesicles (EVs) in plasma from female patients with established rheumatoid arthritis (RA) in relation to the activation of coagulation and fibrin formation in these patients. Forty women were included in the study, 20 patients and 20 age-matched healthy controls. The mean disease duration in patients was 13.0 (5.0–25.0) years, with medium to high disease activity despite ongoing treatment with low-dose prednisolone and methotrexate. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. The concentration of phosphatidylserine-positive (PS+) EVs; platelet (CD42a+), leucocyte (CD45+), monocyte (CD14+), and endothelial (CD144+)-derived EVs; and EVs-expressing tissue factor (CD142+), P-selectin (CD62P+), and E-selectin (CD62E+) were determined by flow cytometry analysis. Overall hemostasis potential (OHP) was assessed to follow the hemostatic disturbances, including the parameters for overall coagulation potential (OCP) and overall fibrinolytic potential (OFP). Fibrin clot turbidity was measured together with clot lysis time, and scanning electron microscopy was performed. Increased concentrations of PS+, CD42a+, CD142+, CD45+, CD14+, and CD62P+ EVs were found in plasma from patients with RA compared to healthy controls, and the concentrations of PS+, CD42a+, CD14+, and CD62P+ EVs were positively correlated with the inflammatory parameters in RA patients. Positive correlations were also found between the levels of PS+ and CD42a+ EVs and OCP as well as between the levels of PS+, CD42a+, and CD62P+EVs and OHP. The levels of PS+, CD42a+, CD14+, CD62P+, and CD62E+ EVs were negatively correlated with OFP. Elevated levels of circulating EVs of different cell origins were found in patients with established RA, in relation to the inflammatory burden and coagulation activation in the disease.
Highlights
Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease causing synovitis and destructive arthritis and is accompanied by out-of-joint disease manifestations, a strong systemic inflammatory response with accelerated development of atherosclerosis and shortened life expectancy and as such represents a significant burden for both individuals and society [1,2,3,4,5]
Considering the above observations, we aimed to identify different subpopulations of extracellular vesicles (EVs) in the plasma of female patients with established RA in relation to the hemostatic disturbances associated with chronic systemic inflammation in this disease
There were no differences between the healthy controls (HCs) and RA patients regarding the presence of traditional cardiovascular disease (CVD) risk factors or regarding lipid profile
Summary
Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease causing synovitis and destructive arthritis and is accompanied by out-of-joint disease manifestations, a strong systemic inflammatory response with accelerated development of atherosclerosis and shortened life expectancy and as such represents a significant burden for both individuals and society [1,2,3,4,5]. The pathogenesis of RA is complex and comprises interactions between genetics, epigenetic modifications, and environmental factors such as smoking, all of which contribute to the production of specific autoantibodies against citrullinated proteins (ACPAs), systemic inflammatory response, and joint destruction. Microparticles, called extracellular vesicles (EVs), are small membrane-coated vesicles 0.1–1.0 μm in diameter that are released from various cells during cell activation and apoptosis. Depending on the cell of origin, EVs incorporate nuclear, cytoplasmic, and membrane molecules as they detach from the cells, and they express cellular antigens on their surface [10]. EVs have important procoagulant properties based on the availability of phosphatidylserine (PS) exposed on the surface after stimulation [13]
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