Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort

Abstract

BackgroundSerpinF2, SerpinG1, CystatinC and CD14 are involved in inflammatory processes and plasma extracellular vesicle (EV) -levels of these proteins have been reported to be associated with systemic vascular events. Evidence is accumulating that inflammatory processes may play a pivotal role both in systemic vascular events and in heart failure. Therefore, we studied the association between plasma extracellular vesicle SerpinF2-, SerpinG1-, CystatinC and CD14-levels and the occurrence of acute heart failure in patients.Methods and ResultExtracellular vesicle protein levels of SerpinG1, SerpinF2, CystatinC and CD14 were measured in an observational study of 404 subjects presenting with dysponea at the emergency department (4B-cohort). Plasma extracellular vesicles were precipitated in a total extracellular vesicles (TEX)-fraction and in separate LDL- and HDL-subfractions. Extracellular vesicle protein levels were measured with a quantitative immune assay in all 3 precipitates. Out of 404 subjects, 141 (35%) were diagnosed with acutely decompensated heart failure. After correction for confounders (including comorbidities and medications), levels of CD14 in the HDL-fraction (OR 1.53, p = 0.01), SerpinF2 in the TEX-and LDL-fraction (ORs respectively 0.71 and 0.65, p<0.05) and SerpinG1 in the TEX-fraction (OR 1.55, p = 0.004) were statistically significantly related to heart failure. Furthermore, extracellular vesicle CD14- and SerpinF2-levels were significantly higher in heart failure patients with preserved ejection fraction than in those with reduced ejection fraction.ConclusionExtracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events.

In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan

“…Finally, IL1A has been proposed as an essential mediator of HF pathogenesis [72,73] through inflammation modulations, and serum levels of this protein have been found increased in MD patients [74]. In addition, as described in previous sections, classifiers FGB, SERPINE1, and SERPING1 have been linked to MD [52][53][54] and are also known to play a role in HF development [75][76][77][78]. According to these findings, the 10 potential biomarkers proposed by TPMS and identified with GUILDify might be prioritized when studying good responder HF patients at risk of MD development.…”

Lowering Low-Density Lipoprotein Particles in Plasma Using Dextran Sulphate Co-Precipitates Procoagulant Extracellular Vesicles

“…Plasma from 20 healthy volunteers (10 male and 10 female, average age 30.3 ± 8.2 years) was used for this study. Blood was collected into ethylenediaminetetraacetic acid (EDTA) tubes and centrifuged at 2000 g for 10 min at 4 °C as previously described [ 40 ]. The plasma was collected and stored at −80 °C for further analysis.…”

“…(V)LDL and HDL fractions were selectively precipitated as previously described [ 40 , 41 ]. Briefly, 6.5% ( w/v ) dextran sulphate (DS) and 2 M Manganese (II) chloride (MnCl 2 ) (Sigma-Aldrich, St. Louis, MO, USA) stock solutions were prepared in Milli-Q H 2 O.…”

Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology

“… 12 This, however, might be used in isolating a subset of EVs co-precipitated with LDL or high density lipoprotein (HDL) particles. 21 , 22 …”