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001     270807
005     20250523100557.0
024 7 _ |a pmc:PMC11264787
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024 7 _ |a 10.1186/s12967-024-05407-0
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037 _ _ |a DZNE-2024-00898
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Talevi, Valentina
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245 _ _ |a Peripheral whole blood microRNA expression in relation to vascular function: a population-based study.
260 _ _ |a London
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|b BioMed Central
336 7 _ |a article
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336 7 _ |a JOURNAL_ARTICLE
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520 _ _ |a 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.
536 _ _ |a 354 - Disease Prevention and Healthy Aging (POF4-354)
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650 _ 7 |a Arterial compliance
|2 Other
650 _ 7 |a Biomarkers
|2 Other
650 _ 7 |a Blood microRNA
|2 Other
650 _ 7 |a Cardiac output
|2 Other
650 _ 7 |a Epigenomics
|2 Other
650 _ 7 |a Population-based
|2 Other
650 _ 7 |a Vascular function
|2 Other
650 _ 7 |a WGCNA
|2 Other
650 _ 7 |a White matter hyperintensity
|2 Other
650 _ 7 |a microRNA-gene regulatory networks
|2 Other
650 _ 7 |a MicroRNAs
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Female
|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 Adult
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Gene Regulatory Networks
|2 MeSH
650 _ 2 |a Gene Expression Regulation
|2 MeSH
650 _ 2 |a Blood Vessels: physiology
|2 MeSH
650 _ 2 |a Cohort Studies
|2 MeSH
650 _ 2 |a Gene Ontology
|2 MeSH
650 _ 2 |a Gene Expression Profiling
|2 MeSH
693 _ _ |0 EXP:(DE-2719)Rhineland Study-20190321
|5 EXP:(DE-2719)Rhineland Study-20190321
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700 1 _ |a Melas, Konstantinos
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700 1 _ |a Pehlivan, Gökhan
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700 1 _ |a Imtiaz, Mohammed A
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700 1 _ |a Krüger, Dennis Manfred
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700 1 _ |a Centeno, Tonatiuh Pena
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700 1 _ |a Aziz, N Ahmad
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700 1 _ |a Fischer, Andre
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700 1 _ |a Breteler, Monique M B
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773 _ _ |a 10.1186/s12967-024-05407-0
|g Vol. 22, no. 1, p. 670
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|t Journal of translational medicine
|v 22
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|x 1479-5876
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