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@ARTICLE{Talevi:270807,
      author       = {Talevi, Valentina and Melas, Konstantinos and Pehlivan,
                      Gökhan and Imtiaz, Mohammed A and Krüger, Dennis Manfred
                      and Centeno, Tonatiuh Pena and Aziz, N Ahmad and Fischer,
                      Andre and Breteler, Monique M B},
      title        = {{P}eripheral whole blood micro{RNA} expression in relation
                      to vascular function: a population-based study.},
      journal      = {Journal of translational medicine},
      volume       = {22},
      number       = {1},
      issn         = {1479-5876},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2024-00898},
      pages        = {670},
      year         = {2024},
      abstract     = {As key regulators of gene expression, microRNAs affect many
                      cardiovascular mechanisms and have been associated with
                      several cardiovascular diseases. In this study, we aimed to
                      investigate the relation of whole blood microRNAs with
                      several quantitative measurements of vascular function, and
                      explore their biological role through an integrative
                      microRNA-gene expression analysis.Peripheral whole blood
                      microRNA expression was assessed through RNA-Seq in 2606
                      participants $(45.8\%$ men, mean age: 53.93, age range: 30
                      to 95 years) from the Rhineland Study, an ongoing
                      population-based cohort study in Bonn, Germany. Weighted
                      gene co-expression network analysis was used to cluster
                      microRNAs with highly correlated expression levels into 14
                      modules. Through linear regression models, we investigated
                      the association between each module's expression and
                      quantitative markers of vascular health, including pulse
                      wave velocity, total arterial compliance index, cardiac
                      index, stroke index, systemic vascular resistance index,
                      reactive skin hyperemia and white matter hyperintensity
                      burden. For each module associated with at least one trait,
                      one or more hub-microRNAs driving the association were
                      defined. Hub-microRNAs were further characterized through
                      mapping to putative target genes followed by gene ontology
                      pathway analysis.Four modules, represented by hub-microRNAs
                      miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p,
                      miR-6786-3p, and miR-330-5p, were associated with total
                      arterial compliance index. Importantly, the miR-320 family
                      module was also associated with white matter hyperintensity
                      burden, an effect partially mediated through arterial
                      compliance. Furthermore, hub-microRNA miR-192-5p was related
                      to cardiac index. Functional analysis corroborated the
                      relevance of the identified microRNAs for vascular function
                      by revealing, among others, enrichment for pathways involved
                      in blood vessel morphogenesis and development, angiogenesis,
                      telomere organization and maintenance, and insulin
                      secretion.We identified several microRNAs robustly
                      associated with cardiovascular function, especially arterial
                      compliance and cardiac output. Moreover, our results
                      highlight miR-320 as a regulator of cerebrovascular damage,
                      partly through modulation of vascular function. As many of
                      these microRNAs were involved in biological processes
                      related to vasculature development and aging, our results
                      contribute to the understanding of vascular physiology and
                      provide putative targets for cardiovascular disease
                      prevention.},
      keywords     = {Humans / Male / Middle Aged / Female / MicroRNAs: blood /
                      MicroRNAs: genetics / Aged / Adult / Aged, 80 and over /
                      Gene Regulatory Networks / Gene Expression Regulation /
                      Blood Vessels: physiology / Cohort Studies / Gene Ontology /
                      Gene Expression Profiling / Arterial compliance (Other) /
                      Biomarkers (Other) / Blood microRNA (Other) / Cardiac output
                      (Other) / Epigenomics (Other) / Population-based (Other) /
                      Vascular function (Other) / WGCNA (Other) / White matter
                      hyperintensity (Other) / microRNA-gene regulatory networks
                      (Other) / MicroRNAs (NLM Chemicals)},
      cin          = {AG Breteler / AG Fischer / Bioinformatics Unit (Göttingen)
                      / AG Aziz},
      ddc          = {610},
      cid          = {I:(DE-2719)1012001 / I:(DE-2719)1410002 /
                      I:(DE-2719)1440016 / I:(DE-2719)5000071},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354) / 352
                      - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-352},
      experiment   = {EXP:(DE-2719)Rhineland Study-20190321},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC11264787},
      pubmed       = {pmid:39030538},
      doi          = {10.1186/s12967-024-05407-0},
      url          = {https://pub.dzne.de/record/270807},
}