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000280784 0247_ $$2doi$$a10.1016/j.cyto.2025.157012
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000280784 0247_ $$2ISSN$$a1096-0023
000280784 037__ $$aDZNE-2025-00968
000280784 041__ $$aEnglish
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000280784 1001_ $$0P:(DE-2719)9001174$$aVan der Auwera, Sandra$$b0$$eFirst author$$udzne
000280784 245__ $$aCirculating miRNAs and inflammatory markers - Associations between miRNAs and cytokine levels point to miRNA-mediated sCD40L release from platelets.
000280784 260__ $$aOxford ˜[u.a.]œ$$bElsevier$$c2025
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000280784 520__ $$aMicroRNAs (miRNAs) are gaining increasing attention, particularly because of their involvement in immune-related signaling pathways. We investigated the association between 179 plasma-circulating miRNAs (Plasma Focus microRNA PCR Panel) and 47 cytokines ('MILLIPLEX® panel) in 692 participants of the population-based SHIP-TREND cohort (age range 21-79) and two additional cohorts to present a comprehensive map of miRNA-cytokine relations. Multivariate linear regression models identified Bonferroni-corrected significant associations between miRNAs and cytokines for EGF (pro-epidermal growth factor), PDGF-AA, PDGF-AB/BB (platelet-derived growth factor subunit A and B), VEGF-A (vascular endothelia growth factor A), and sCD40L (soluble CD40 ligand) with sCD40L showing the most robust pattern. These models were adjusted for age, sex, platelet count, BMI, smoking, and technical parameters. In the follow-up sample (N = 191, 7 years after initial sampling), we confirmed that the observed associations were stable over time and replicated our findings in an independent clinical cohort (N = 74). Furthermore, the causal mediation results provide evidence for the involvement of platelet activity in the regulation of sCD40L mediated by five miRNAs in the range of 25 %-69 % of the effect being mediated (strongest mediation for hsa-miR-223-3p). Our study highlights a strong and stable miRNA-mediated modulation of sCD40L, at the stage of platelet activation with potential subsequent effects on the interaction of immune cells and haemostasis pointing to a complex regulatory mechanism. Future research is needed to determine the clinical relevance of our observations in the context of vascular thrombosis, immunological disorders, and neurodegeneration.
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000280784 650_7 $$2Other$$aCirculating biomarkers
000280784 650_7 $$2Other$$aPlatelet activation
000280784 650_7 $$2Other$$aSHIP study
000280784 650_7 $$2Other$$amiRNA mediated sCD40L release
000280784 650_7 $$2Other$$amiRNA-cytokine association
000280784 650_7 $$0147205-72-9$$2NLM Chemicals$$aCD40 Ligand
000280784 650_7 $$2NLM Chemicals$$aCytokines
000280784 650_7 $$2NLM Chemicals$$aMicroRNAs
000280784 650_7 $$2NLM Chemicals$$aBiomarkers
000280784 650_7 $$2NLM Chemicals$$aCirculating MicroRNA
000280784 650_2 $$2MeSH$$aHumans
000280784 650_2 $$2MeSH$$aCD40 Ligand: blood
000280784 650_2 $$2MeSH$$aCD40 Ligand: metabolism
000280784 650_2 $$2MeSH$$aMale
000280784 650_2 $$2MeSH$$aFemale
000280784 650_2 $$2MeSH$$aMiddle Aged
000280784 650_2 $$2MeSH$$aBlood Platelets: metabolism
000280784 650_2 $$2MeSH$$aAdult
000280784 650_2 $$2MeSH$$aCytokines: blood
000280784 650_2 $$2MeSH$$aMicroRNAs: blood
000280784 650_2 $$2MeSH$$aMicroRNAs: genetics
000280784 650_2 $$2MeSH$$aAged
000280784 650_2 $$2MeSH$$aBiomarkers: blood
000280784 650_2 $$2MeSH$$aCirculating MicroRNA: blood
000280784 650_2 $$2MeSH$$aCirculating MicroRNA: genetics
000280784 650_2 $$2MeSH$$aInflammation: blood
000280784 650_2 $$2MeSH$$aYoung Adult
000280784 650_2 $$2MeSH$$aCohort Studies
000280784 7001_ $$aAmeling, Sabine$$b1
000280784 7001_ $$aWiechert, Anja$$b2
000280784 7001_ $$aFriedrich, Nele$$b3
000280784 7001_ $$aNauck, Matthias$$b4
000280784 7001_ $$aVölzke, Henry$$b5
000280784 7001_ $$aBröker, Barbara M$$b6
000280784 7001_ $$0P:(DE-2719)2811781$$aGrabe, Hans J$$b7$$udzne
000280784 7001_ $$aVölker, Uwe$$b8
000280784 773__ $$0PERI:(DE-600)1463198-2$$a10.1016/j.cyto.2025.157012$$gVol. 194, p. 157012 -$$p157012$$tCytokine$$v194$$x1043-4666$$y2025
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