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000270807 1001_ $$0P:(DE-2719)9001002$$aTalevi, Valentina$$b0$$eFirst author$$udzne
000270807 245__ $$aPeripheral whole blood microRNA expression in relation to vascular function: a population-based study.
000270807 260__ $$aLondon$$bBioMed Central$$c2024
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000270807 520__ $$aAs 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.
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000270807 650_7 $$2Other$$aArterial compliance
000270807 650_7 $$2Other$$aBiomarkers
000270807 650_7 $$2Other$$aBlood microRNA
000270807 650_7 $$2Other$$aCardiac output
000270807 650_7 $$2Other$$aEpigenomics
000270807 650_7 $$2Other$$aPopulation-based
000270807 650_7 $$2Other$$aVascular function
000270807 650_7 $$2Other$$aWGCNA
000270807 650_7 $$2Other$$aWhite matter hyperintensity
000270807 650_7 $$2Other$$amicroRNA-gene regulatory networks
000270807 650_7 $$2NLM Chemicals$$aMicroRNAs
000270807 650_2 $$2MeSH$$aHumans
000270807 650_2 $$2MeSH$$aMale
000270807 650_2 $$2MeSH$$aMiddle Aged
000270807 650_2 $$2MeSH$$aFemale
000270807 650_2 $$2MeSH$$aMicroRNAs: blood
000270807 650_2 $$2MeSH$$aMicroRNAs: genetics
000270807 650_2 $$2MeSH$$aAged
000270807 650_2 $$2MeSH$$aAdult
000270807 650_2 $$2MeSH$$aAged, 80 and over
000270807 650_2 $$2MeSH$$aGene Regulatory Networks
000270807 650_2 $$2MeSH$$aGene Expression Regulation
000270807 650_2 $$2MeSH$$aBlood Vessels: physiology
000270807 650_2 $$2MeSH$$aCohort Studies
000270807 650_2 $$2MeSH$$aGene Ontology
000270807 650_2 $$2MeSH$$aGene Expression Profiling
000270807 693__ $$0EXP:(DE-2719)Rhineland Study-20190321$$5EXP:(DE-2719)Rhineland Study-20190321$$eRhineland Study / Bonn$$x0
000270807 7001_ $$0P:(DE-2719)9001389$$aMelas, Konstantinos$$b1$$udzne
000270807 7001_ $$0P:(DE-2719)2811125$$aPehlivan, Gökhan$$b2$$udzne
000270807 7001_ $$0P:(DE-2719)9002347$$aImtiaz, Mohammed A$$b3$$udzne
000270807 7001_ $$0P:(DE-2719)2812548$$aKrüger, Dennis Manfred$$b4$$udzne
000270807 7001_ $$0P:(DE-2719)2811063$$aCenteno, Tonatiuh Pena$$b5$$udzne
000270807 7001_ $$0P:(DE-2719)2812578$$aAziz, N Ahmad$$b6$$udzne
000270807 7001_ $$0P:(DE-2719)2000047$$aFischer, Andre$$b7$$udzne
000270807 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique M B$$b8$$eLast author
000270807 773__ $$0PERI:(DE-600)2118570-0$$a10.1186/s12967-024-05407-0$$gVol. 22, no. 1, p. 670$$n1$$p670$$tJournal of translational medicine$$v22$$x1479-5876$$y2024
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