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- Colic, J, et al.
(author)
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EXTRACELLULAR VESICLES AS POTENTIAL BIOMARKERS OF EARLY DISEASE STAGE IN SYSTEMIC SCLEROSIS
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 761-761
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Conference paper (other academic/artistic)abstract
- Extracellular vesicles (EVs) are membrane-coated vesicles most often generated from the vasculature and circulating blood cells upon cell activation and during the early phase of apoptosis (1).ObjectivesTo evaluate the concentration of different subpopulations of EVs in plasma from patients with SSc in relation to the disease duration and to the markers of endothelial injury.MethodsOur study included 59 SSc patients (36 limited (lSSc) and 23 diffuse cutaneous subset (dSSc)) and 46 healthy age and gender matched controls subjects. Disease duration less than 3 years in patients with dSSc and less than 5 years in those with lSSc was considered as early disease stage. Clinical evaluation of patients was performed. EVs were analysed with flow cytometry after staining platelet poor plasma with fluorescent cell-specific monoclonal antibodies. The concentration of following phosphatidylserine-positive EVs (PS+ EVs) were analyzed: total EVs, endothelial EVs (EEVs; CD144+), platelet EVs (PEVs; CD42b+), monocytes EVs (LEVs; CD14+), EVs expressing ICAM1 (CD54+), VCAM1 (CD106+) and P selectin (CD62p+). Serum levels of ICAM1, VCAM1 and P selectin were determined with ELISA.ResultsMedian disease duration of our cohort was 4 (0-29) years (early lSSc [20/36]: 2.5 (0-4.5) years; early dSSc [11/23]: 10 (1-30) months). All types of investigated EVs were significantly elevated in SSc patients compared to controls (p<0.05). Patients with early disease stage had significantly increased levels of all PS+EVs compared to HC (p<0.05). Moreover, the levels of EVs expressing ICAM1 and VCAM1 showed good validity in identifying patients with early disease stage (AUC 0.7, p<0.01). PEVs were increased in early dSSc compared to early lSSc, but the difference did not reach statistical significance (p=0.07). There was a correlation between serum levels and the levels of EVs expressing specific adhesion molecules (ICAM1: r=0.7, p<0.01; VCAM1: r=0.7, p<0.01; P selectin: r=-0.7, p<0.01), only within the group with early dSSc subtype of the disease. Further correlations were detected between ICAM1+EVs with either mRSS (r=0.07, p< 0.01) or EUSTAR activity index (r=0.07, p= 0.02) among patients with early dSSc.ConclusionIncreased levels of circulating EVs of different cell origin were present in patients with early SSc. EVs expressing either ICAM1 or VCAM1 could be novel biomarkers of early disease. EVs expressing ICAM1 showed association with severity of skin involvement and disease activity in patients with early dSSc giving insight into their role in the pathogenesis of SSc.References[1]J Colic, M Matucci-Cerinic, S Guiducci and N Damjanov. Review: Microparticles in systemic sclerosis, targets or tools to control fibrosis: This is the question!. Journal of Scleroderma and Related Disorders. 2019; 5(34):239719831985735Disclosure of InterestsNone declared
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- Zong, Y., et al.
(author)
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Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models
- 2020
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In: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation. We investigated if MPs improve hemostasis in HA plasma models. MPs isolated from pooled normal human plasma were added to severe, moderate and mild HA plasma models (0%, 2.5%, 20% FVIII). The MPs’ effect on hemostasis was evaluated by calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP) assays, while fibrin structure was imaged by standard confocal, stimulated emission depletion (STED) microscopy and scanning electron microscopy (SEM). MPs partially restored thrombin generation and fibrin formation in all HA plasma models. The procoagulant effect of MPs requires PS exposure, to a less extent of contact pathway activation, but not tissue factor exposure or in vitro stimulation of MPs. MPs partially normalized the fibrin structure, and using super-resolution STED, MPs attached to fibrin were clearly resolved. In summary, our results demonstrate that PS positive MPs could improve hemostasis in HA plasma models.
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