Alterations in Circulating MicroRNAs and the Relation of MicroRNAs to Maximal Oxygen Consumption and Intima–Media Thickness in Ultra-Marathon Runners

Eyileten, Ceren; Fitas, Alex; Jakubik, Daniel; Czajka, Pamela; Mróz, Anna; Czajkowska, Anna; Witek, Katarzyna; Bakalarski, Wawrzyniec; Rosa, Salvatore De; Postuła, Marek; Małek, Łukasz A.

doi:10.3390/ijerph18147234

Cited by 11 publications

(5 citation statements)

References 69 publications

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“…During the RNA extraction phase cel-miR-39 was spiked-in as an exogenous control and all qRT-PCRs were normalized to their corresponding cel-miR-39. Reactions were run in triplicate and miRNA expressions were expressed as 2-∆CT [25,75].…”

Section: Rna Preparation Detection and Quantification Of Mirnas By Qu...mentioning

confidence: 99%

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

Eyileten

Jakubik

Shahzadi

et al. 2022

IJMS

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Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics.

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Section: Rna Preparation Detection and Quantification Of Mirnas By Qu...mentioning

confidence: 99%

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

Eyileten

Jakubik

Shahzadi

et al. 2022

IJMS

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“…The HUNT study revealed that increased levels of miR-125a were associated with low VO 2 max in male participants, which is an indicator of cardiopulmonary fitness ( Bye et al, 2013 ). In our previous study we also found that the ultramarathon runners with the highest quartile of VO 2 max had a lower expression of miR-125a-5p ( Eyileten et al, 2021 ). In the current study we observed a negative correlation between miR-125a-5p and maximum lactate concentration.…”

Section: Discussionmentioning

confidence: 79%

Altered Circulating MicroRNA Profiles After Endurance Training: A Cohort Study of Ultramarathon Runners

et al. 2022

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BackgroundDespite the positive effects of endurance training on the cardiovascular (CV) system, excessive exercise induces not only physiological adaptations but also adverse changes in CV system, including the heart. We aimed to evaluate the selected miRNAs expression based on bioinformatic analysis and their changes before and after an ultramarathon run.Materials and MethodsCardiac tissue-specific targets were identified with the Tissue 2.0 database. Gene-gene interaction data were retrieved from the STRING app for Cytoscape. Twenty-three endurance athletes were recruited to the study. Athletes ran to completion (100 km) or exhaustion (52–91 km, median 74 km). All participants completed pre- and post-run testing. miRNAs expressions were measured both before and after the race.ResultsEnrichment analysis of the signaling pathways associated with the genes targeted by miRNAs selected for qRT-PCR validation (miR-1-3p, miR-126, miR-223, miR-125a-5p, miR-106a-5p, and miR-15a/b). All selected miRNAs showed overlap in regulation in pathways associated with cancer, IL-2 signaling, TGF-β signaling as well as BDNF signaling pathway. Analysis of metabolites revealed significant regulation of magnesium and guanosine triphosphate across analyzed miRNA targets. MiR-1-3p, miR-125a-5p, miR-126, and miR-223 expressions were measured in 23 experienced endurance athletes, before and after an ultramarathon wherein athletes ran to completion (100 km) or exhaustion (52–91 km, median 74 km). The expressions of miR-125a-5p, miR-126, and miR-223 were significantly increased after the race (p = 0.007, p = 0.001, p = 0.014, respectively). MiR-1-3p expression post-run showed a negative correlation with the post-run levels of high-sensitivity C-reactive protein (hs-CRP) (r = −0.632, p = 0.003). Higher miR-1-3p expression was found in runners, who finished the race under 10 h compared to runners who finished over 10 h (p = 0.001). Post-run miR-125a-5p expression showed a negative correlation with the peak lactate during the run (r = −0.576, p = 0.019).ConclusionExtreme physical activity, as exemplified by an ultramarathon, is associated with changes in circulating miRNAs’ expression related to inflammation, fibrosis, and cardiac muscle function. In particular, the negative correlations between miR-125a-5p and lactate concentrations, and miR-1-3p and hs-CRP, support their role in specific exercise-induced adaptation. Further studies are essential to validate the long-term effect of these observations.

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“…Future research should expand to multicentric studies with larger, more diverse populations to confirm these findings and investigate the physiological mechanisms underlying the observed effects. Investigating whether cessation of SLT/Naswar use prior to interventions affects outcomes would also be valuable (18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Incidence of Ischemic Heart Disease (IHD) in Smokeless Tobacco/Naswar Users Versus Non-Users Following Coronary Interventions

Khan,

Memon,

Rehmat

et al. 2024

JHRR

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Background: Ischemic heart disease (IHD) is a significant health concern globally, with various risk factors affecting the outcomes of therapeutic interventions like percutaneous coronary interventions (PCIs) and coronary artery bypass grafting (CABG). The use of smokeless tobacco products such as SLT (snus, loose snuff) and Naswar is prevalent in South Asia and poses additional risks due to its cardiovascular implications. Objective: This study aims to assess the impact of smokeless tobacco (SLT/Naswar) use on the incidence of IHD following coronary interventions, highlighting the need for tailored healthcare strategies to address this modifiable risk factor. Methods: A prospective observational study was conducted from July 1, 2023, to January 1, 2024, involving 200 participants aged 18 to 80 years diagnosed with IHD. Data collection involved structured interviews and comprehensive reviews of health records. Statistical analyses included Chi-square tests and logistic regression to evaluate the association between SLT/Naswar usage and IHD incidence post-intervention, with SPSS software utilized for all computations. Results: Among the participants, 40.5% were users of SLT/Naswar. Post-coronary intervention, SLT/Naswar users showed a 66% incidence rate of IHD compared to 48% in non-users, with a statistically significant difference (P=0.032). Successful intervention rates were 62% in SLT/Naswar users versus 78% in non-users. Complication rates such as re-stenosis were higher in SLT/Naswar users (29% vs. 16%). Conclusion: The study demonstrates that SLT/Naswar use significantly impacts the outcomes of coronary interventions, with a higher incidence of IHD and complications among users. These findings underscore the importance of integrating smokeless tobacco cessation programs into cardiovascular care protocols.

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Alterations in Circulating MicroRNAs and the Relation of MicroRNAs to Maximal Oxygen Consumption and Intima–Media Thickness in Ultra-Marathon Runners

Cited by 11 publications

References 69 publications

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

Diagnostic Performance of Circulating miRNAs and Extracellular Vesicles in Acute Ischemic Stroke

Altered Circulating MicroRNA Profiles After Endurance Training: A Cohort Study of Ultramarathon Runners

Incidence of Ischemic Heart Disease (IHD) in Smokeless Tobacco/Naswar Users Versus Non-Users Following Coronary Interventions

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