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@ARTICLE{VanderAuwera:280784,
      author       = {Van der Auwera, Sandra and Ameling, Sabine and Wiechert,
                      Anja and Friedrich, Nele and Nauck, Matthias and Völzke,
                      Henry and Bröker, Barbara M and Grabe, Hans J and Völker,
                      Uwe},
      title        = {{C}irculating mi{RNA}s and inflammatory markers -
                      {A}ssociations between mi{RNA}s and cytokine levels point to
                      mi{RNA}-mediated s{CD}40{L} release from platelets.},
      journal      = {Cytokine},
      volume       = {194},
      issn         = {1043-4666},
      address      = {Oxford ˜[u.a.]œ},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00968},
      pages        = {157012},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / CD40 Ligand: blood / CD40 Ligand: metabolism /
                      Male / Female / Middle Aged / Blood Platelets: metabolism /
                      Adult / Cytokines: blood / MicroRNAs: blood / MicroRNAs:
                      genetics / Aged / Biomarkers: blood / Circulating MicroRNA:
                      blood / Circulating MicroRNA: genetics / Inflammation: blood
                      / Young Adult / Cohort Studies / Circulating biomarkers
                      (Other) / Platelet activation (Other) / SHIP study (Other) /
                      miRNA mediated sCD40L release (Other) / miRNA-cytokine
                      association (Other) / CD40 Ligand (NLM Chemicals) /
                      Cytokines (NLM Chemicals) / MicroRNAs (NLM Chemicals) /
                      Biomarkers (NLM Chemicals) / Circulating MicroRNA (NLM
                      Chemicals)},
      cin          = {AG Grabe},
      ddc          = {570},
      cid          = {I:(DE-2719)5000001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40803257},
      doi          = {10.1016/j.cyto.2025.157012},
      url          = {https://pub.dzne.de/record/280784},
}