Untargeted sequencing of circulating microRNAs in a healthy and diseased older population

Streese, Lukas; Demougin, Philippe; Iborra, Paula; Kanitz, Alexander; Deiseroth, Arne; Kröpfl, Julia M.; Schmidt‐Trucksäss, Arno; Zavolan, Mihaela; Hanssen, Henner

doi:10.1038/s41598-022-06956-4

Cited by 6 publications

(5 citation statements)

References 66 publications

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“…Although previous studies have reported associations of the identified miRNAs with impaired glucose metabolism, lipid metabolism, and cardiac dysfunction, the plasma miRNA signatures of CVD risk factors have not been fully elucidated at a population level in middle‐age or older individuals. 17 , 51 , 63 , 65 , 66 , 67 To that end, we elucidated miRNA signatures of CVD risk factors and replicated a subset of these miRNAs in an independent population‐based cohort study. We identified 6 miRNAs (miR‐193b‐3p, miR‐122‐5p, miR‐365a‐3p, miR‐194‐5p, miR‐192‐5p, and miR‐193a‐5p) that were associated with 5 or more CVD risk factors in the FHS.…”

Section: Discussionmentioning

confidence: 96%

“…conducted untargeted sequencing of miRNAs from serum in 158 older participants who were healthy or had disease, revealing 30 circulating miRNAs associated with cardiovascular health and physical activity or disease. 51 Mens et al. identified 22 plasma miRNAs associated with at least 1 cardiometabolic trait and further reported 4 miRNAs to be strongly linked to lipid traits following multiomic analysis.…”

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confidence: 99%

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Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle‐Aged and Older Adults

Karlin,

Sooda,

Larson

et al. 2024

JAHA

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Background Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level. Methods and Results Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants. Linear regression analyses were conducted to test the cross‐sectional associations of each miRNA with 8 CVD risk factors. Prospective analyses of the associations of miRNAs with new‐onset obesity, hypertension, type 2 diabetes, CVD, and all‐cause mortality were conducted using proportional hazards regression. Replication was carried out in 1999 RS (Rotterdam Study) participants. Pathway enrichment analyses were conducted and target genes were predicted for miRNAs associated with ≥5 risk factors in the FHS. In the FHS, 6 miRNAs (miR‐193b‐3p, miR‐122‐5p, miR‐365a‐3p, miR‐194‐5p, miR‐192‐5p, and miR‐193a‐5p) were associated with ≥5 risk factors. This miRNA signature was enriched for pathways associated with CVD and several genes annotated to these pathways were predicted targets of the identified miRNAs. Furthermore, miR‐193b‐3p, miR‐194‐5p, and miR‐193a‐5p were each associated with ≥2 risk factors in the RS. Prospective analysis revealed 8 miRNAs associated with all‐cause mortality in the FHS. Conclusions These findings highlight associations between miRNAs and CVD risk factors that may provide valuable insights into the underlying pathogenesis of CVD.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle‐Aged and Older Adults

Karlin,

Sooda,

Larson

et al. 2024

JAHA

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“…None of the plasma miRs described by Estebanez et al matched with our 15 significantly changed miRs in exosomes from patient derived myotubes ( Estebanez et al, 2021 ). MiR-92b-5p might also be interesting, since it recently showed higher expression in healthy active individuals than in sedentary individuals ( Streese et al, 2022 ), indicating a role in physical activity/exercise. MiR-1233-5p was the miR most changed by EPS in our study, and the highly predicted target protein S100A7 was the protein most reduced after EPS.…”

Section: Discussionmentioning

confidence: 99%

Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation

et al. 2023

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Lifestyle disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases can be prevented and treated by regular physical activity. During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from six morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter. Size and concentration of EV subtypes were characterized by nanoparticle tracking analysis, surface markers were examined by flow cytometry and Western blotting, and morphology was confirmed by transmission electron microscopy. Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix microarray, and selected microRNAs (miRs) validated by real time RT-qPCR. The size and concentration of exosomes and MV were unaffected by EPS. Of the 400 miRs identified in the EVs, EPS significantly changed the level of 15 exosome miRs, of which miR-1233-5p showed the highest fold change. The miR pattern of MV was unaffected by EPS. Totally, about 1000 proteins were identified in exosomes and 2000 in MV. EPS changed the content of 73 proteins in exosomes, 97 in MVs, and of these four were changed in both exosomes and MV (GANAB, HSPA9, CNDP2, and ATP5B). By matching the EPS-changed miRs and proteins in exosomes, 31 targets were identified, and among these several promising signaling factors. Of particular interest were CNDP2, an enzyme that generates the appetite regulatory metabolite Lac-Phe, and miR-4433b-3p, which targets CNDP2. Several of the regulated miRs, such as miR-92b-5p, miR-320b, and miR-1233-5p might also mediate interesting signaling functions. In conclusion, we have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of EVs derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.

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“…Regulating neuronal cell injury [54] Serum biomarker for AD [55] Upregulated in AD [56] Associated with higher metabolic risk profile in older subjects [57] hsa-miR-199a-5p…”

Section: Hsa-mir-885-5pmentioning

confidence: 99%

“…Association with WML and cognitive impairment [16] Associated with higher metabolic risk profile in older subjects [57] Downregulated in blood of AD patients [62] Inhibit apoptosis of hippocampal neurons [63] hsa-miR-140-5p…”

Section: Hsa-mir-885-5pmentioning

confidence: 99%

Circulating microRNA miR-425-5p Associated with Brain White Matter Lesions and Inflammatory Processes

Van der Auwera,

Ameling,

Wittfeld

et al. 2024

IJMS

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White matter lesions (WML) emerge as a consequence of vascular injuries in the brain. While they are commonly observed in aging, associations have been established with neurodegenerative and neurological disorders such as dementia or stroke. Despite substantial research efforts, biological mechanisms are incomplete and biomarkers indicating WMLs are lacking. Utilizing data from the population-based Study of Health in Pomerania (SHIP), our objective was to identify plasma-circulating micro-RNAs (miRNAs) associated with WMLs, thus providing a foundation for a comprehensive biological model and further research. In linear regression models, direct association and moderating factors were analyzed. In 648 individuals, we identified hsa-miR-425-5p as directly associated with WMLs. In subsequent analyses, hsa-miR-425-5p was found to regulate various genes associated with WMLs with particular emphasis on the SH3PXD2A gene. Furthermore, miR-425-5p was found to be involved in immunological processes. In addition, noteworthy miRNAs associated with WMLs were identified, primarily moderated by the factors of sex or smoking status. All identified miRNAs exhibited a strong over-representation in neurodegenerative and neurological diseases. We introduced hsa-miR-425-5p as a promising candidate in WML research probably involved in immunological processes. Mir-425-5p holds the potential as a biomarker of WMLs, shedding light on potential mechanisms and pathways in vascular dementia.

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Untargeted sequencing of circulating microRNAs in a healthy and diseased older population

Cited by 6 publications

References 66 publications

Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle‐Aged and Older Adults

Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle‐Aged and Older Adults

Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation

Circulating microRNA miR-425-5p Associated with Brain White Matter Lesions and Inflammatory Processes

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