001     280784
005     20250905102147.0
024 7 _ |a 10.1016/j.cyto.2025.157012
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024 7 _ |a 1096-0023
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037 _ _ |a DZNE-2025-00968
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Van der Auwera, Sandra
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245 _ _ |a Circulating miRNAs and inflammatory markers - Associations between miRNAs and cytokine levels point to miRNA-mediated sCD40L release from platelets.
260 _ _ |a Oxford ˜[u.a.]œ
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520 _ _ |a MicroRNAs (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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650 _ 7 |a Circulating biomarkers
|2 Other
650 _ 7 |a Platelet activation
|2 Other
650 _ 7 |a SHIP study
|2 Other
650 _ 7 |a miRNA mediated sCD40L release
|2 Other
650 _ 7 |a miRNA-cytokine association
|2 Other
650 _ 7 |a CD40 Ligand
|0 147205-72-9
|2 NLM Chemicals
650 _ 7 |a Cytokines
|2 NLM Chemicals
650 _ 7 |a MicroRNAs
|2 NLM Chemicals
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Circulating MicroRNA
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a CD40 Ligand: blood
|2 MeSH
650 _ 2 |a CD40 Ligand: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Blood Platelets: metabolism
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Cytokines: blood
|2 MeSH
650 _ 2 |a MicroRNAs: blood
|2 MeSH
650 _ 2 |a MicroRNAs: genetics
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Biomarkers: blood
|2 MeSH
650 _ 2 |a Circulating MicroRNA: blood
|2 MeSH
650 _ 2 |a Circulating MicroRNA: genetics
|2 MeSH
650 _ 2 |a Inflammation: blood
|2 MeSH
650 _ 2 |a Young Adult
|2 MeSH
650 _ 2 |a Cohort Studies
|2 MeSH
700 1 _ |a Ameling, Sabine
|b 1
700 1 _ |a Wiechert, Anja
|b 2
700 1 _ |a Friedrich, Nele
|b 3
700 1 _ |a Nauck, Matthias
|b 4
700 1 _ |a Völzke, Henry
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700 1 _ |a Bröker, Barbara M
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700 1 _ |a Grabe, Hans J
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700 1 _ |a Völker, Uwe
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773 _ _ |a 10.1016/j.cyto.2025.157012
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