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Circulating microRNAs and aerobic fitness--the HUNT-Study.

Bye A, Røsjø H, Aspenes ST, Condorelli G, Omland T, Wisløff U - PLoS ONE (2013)

Bottom Line: Candiate miRs were validated in a second cohort of subjects with high (n = 38) or low (n = 38) VO2max. miR-210 and miR-222 were found to be higher in the low VO2max-group (p<0.05).In conclusion, we found that miR-210, miR-21, and miR-222 were increased in healthy subjects with low VO2max.The lack of association between these three miRs, and other fitness related variables as well as traditional CVD risk factors, suggests that these miRs may have a potential as new independent biomarkers of fitness level and future CVD.

View Article: PubMed Central - PubMed

Affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Anja.Bye@ntnu.no

ABSTRACT
Aerobic fitness, measured as maximal oxygen uptake (VO2max), is a good indicator of cardiovascular health, and a strong predictor of cardiovascular mortality. Biomarkers associated with low VO2max may therefore represent potential early markers of future cardiovascular disease (CVD). The aim of this study was to assess whether circulating microRNAs (miRs) are associated with VO2max-level in healthy individuals. In a screening study, 720 miRs were measured in serum samples from healthy individuals (40-45 yrs) with high (n = 12) or low (n = 12) VO2max matched for gender, age and physical activity. Candiate miRs were validated in a second cohort of subjects with high (n = 38) or low (n = 38) VO2max. miR-210 and miR-222 were found to be higher in the low VO2max-group (p<0.05). In addition, miR-21 was increased in male participants with low VO2max (p<0.05). There were no correlations between traditional risk factors for CVD (blood pressure, cholesterol, smoking habit, or obesity) and miR-21, miR-210 and miR-222. DIANA-mirPath identified 611 potential gene-targets of miR-21, miR-210 and miR-222, and pathway analysis indicated alterations in several important signaling systems in subjects with low VO2max. Potential bias involve that blood was collected from non-fasting individuals, and that 8 performed exercise within 24 h before sampling. In conclusion, we found that miR-210, miR-21, and miR-222 were increased in healthy subjects with low VO2max. The lack of association between these three miRs, and other fitness related variables as well as traditional CVD risk factors, suggests that these miRs may have a potential as new independent biomarkers of fitness level and future CVD.

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Related in: MedlinePlus

Potentially increased microRNAs and associated pathways in subjects with low maximal oxygen uptake (VO2max).The connections between the biological processes, microRNAs and the regulated pathways in A) the vessel wall and (B) the heart are based on the current knowledge in the literature. Red boxes illustrate the microRNAs that were increased in patients with low VO2max and the yellow boxes depict the associated pathways as identified by miR-Path analyses. Upward arrows inside the boxes illustrate up-regulation and downward arrows illustrate down-regulation. Blue dashed lines indicate the putative release of the microRNAs to the circulation. Pointed arrows illustrate activation and flat arrows illustrate inhibition. c-miR: Circulating microRNA, VEGF: Vascular endothelial growth factor, VO2max: Maximal oxygen uptake.
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pone-0057496-g003: Potentially increased microRNAs and associated pathways in subjects with low maximal oxygen uptake (VO2max).The connections between the biological processes, microRNAs and the regulated pathways in A) the vessel wall and (B) the heart are based on the current knowledge in the literature. Red boxes illustrate the microRNAs that were increased in patients with low VO2max and the yellow boxes depict the associated pathways as identified by miR-Path analyses. Upward arrows inside the boxes illustrate up-regulation and downward arrows illustrate down-regulation. Blue dashed lines indicate the putative release of the microRNAs to the circulation. Pointed arrows illustrate activation and flat arrows illustrate inhibition. c-miR: Circulating microRNA, VEGF: Vascular endothelial growth factor, VO2max: Maximal oxygen uptake.

Mentions: The pathway analysis also predicted that miR-21, miR-210 and miR-222 inhibit the expression of several key proteins in more general pathways associated with growth and development (MAPK, TGF-β, mTOR, ErbB and the Wnt pathways), the immune system (T and B cell signaling) and stress (p53 pathway). Potentially induced pathways in the vessel wall and the heart of subjects with low VO2max are illustrated in Figure 3. The implications of this for the pathophysiology of subjects with low VO2max is not clear and will need more detailed studies of specific pathways. We also acknowledge that currently only limited information is available regarding the origin of circulating miRs. Hence, extrapolating from miRs in the peripheral blood to functional aspects in specific organs should be done with caution. Still, the association to hypoxia- and angiogenesis-related pathways seems interesting and should be further explored.


Circulating microRNAs and aerobic fitness--the HUNT-Study.

Bye A, Røsjø H, Aspenes ST, Condorelli G, Omland T, Wisløff U - PLoS ONE (2013)

Potentially increased microRNAs and associated pathways in subjects with low maximal oxygen uptake (VO2max).The connections between the biological processes, microRNAs and the regulated pathways in A) the vessel wall and (B) the heart are based on the current knowledge in the literature. Red boxes illustrate the microRNAs that were increased in patients with low VO2max and the yellow boxes depict the associated pathways as identified by miR-Path analyses. Upward arrows inside the boxes illustrate up-regulation and downward arrows illustrate down-regulation. Blue dashed lines indicate the putative release of the microRNAs to the circulation. Pointed arrows illustrate activation and flat arrows illustrate inhibition. c-miR: Circulating microRNA, VEGF: Vascular endothelial growth factor, VO2max: Maximal oxygen uptake.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585333&req=5

pone-0057496-g003: Potentially increased microRNAs and associated pathways in subjects with low maximal oxygen uptake (VO2max).The connections between the biological processes, microRNAs and the regulated pathways in A) the vessel wall and (B) the heart are based on the current knowledge in the literature. Red boxes illustrate the microRNAs that were increased in patients with low VO2max and the yellow boxes depict the associated pathways as identified by miR-Path analyses. Upward arrows inside the boxes illustrate up-regulation and downward arrows illustrate down-regulation. Blue dashed lines indicate the putative release of the microRNAs to the circulation. Pointed arrows illustrate activation and flat arrows illustrate inhibition. c-miR: Circulating microRNA, VEGF: Vascular endothelial growth factor, VO2max: Maximal oxygen uptake.
Mentions: The pathway analysis also predicted that miR-21, miR-210 and miR-222 inhibit the expression of several key proteins in more general pathways associated with growth and development (MAPK, TGF-β, mTOR, ErbB and the Wnt pathways), the immune system (T and B cell signaling) and stress (p53 pathway). Potentially induced pathways in the vessel wall and the heart of subjects with low VO2max are illustrated in Figure 3. The implications of this for the pathophysiology of subjects with low VO2max is not clear and will need more detailed studies of specific pathways. We also acknowledge that currently only limited information is available regarding the origin of circulating miRs. Hence, extrapolating from miRs in the peripheral blood to functional aspects in specific organs should be done with caution. Still, the association to hypoxia- and angiogenesis-related pathways seems interesting and should be further explored.

Bottom Line: Candiate miRs were validated in a second cohort of subjects with high (n = 38) or low (n = 38) VO2max. miR-210 and miR-222 were found to be higher in the low VO2max-group (p<0.05).In conclusion, we found that miR-210, miR-21, and miR-222 were increased in healthy subjects with low VO2max.The lack of association between these three miRs, and other fitness related variables as well as traditional CVD risk factors, suggests that these miRs may have a potential as new independent biomarkers of fitness level and future CVD.

View Article: PubMed Central - PubMed

Affiliation: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Anja.Bye@ntnu.no

ABSTRACT
Aerobic fitness, measured as maximal oxygen uptake (VO2max), is a good indicator of cardiovascular health, and a strong predictor of cardiovascular mortality. Biomarkers associated with low VO2max may therefore represent potential early markers of future cardiovascular disease (CVD). The aim of this study was to assess whether circulating microRNAs (miRs) are associated with VO2max-level in healthy individuals. In a screening study, 720 miRs were measured in serum samples from healthy individuals (40-45 yrs) with high (n = 12) or low (n = 12) VO2max matched for gender, age and physical activity. Candiate miRs were validated in a second cohort of subjects with high (n = 38) or low (n = 38) VO2max. miR-210 and miR-222 were found to be higher in the low VO2max-group (p<0.05). In addition, miR-21 was increased in male participants with low VO2max (p<0.05). There were no correlations between traditional risk factors for CVD (blood pressure, cholesterol, smoking habit, or obesity) and miR-21, miR-210 and miR-222. DIANA-mirPath identified 611 potential gene-targets of miR-21, miR-210 and miR-222, and pathway analysis indicated alterations in several important signaling systems in subjects with low VO2max. Potential bias involve that blood was collected from non-fasting individuals, and that 8 performed exercise within 24 h before sampling. In conclusion, we found that miR-210, miR-21, and miR-222 were increased in healthy subjects with low VO2max. The lack of association between these three miRs, and other fitness related variables as well as traditional CVD risk factors, suggests that these miRs may have a potential as new independent biomarkers of fitness level and future CVD.

Show MeSH
Related in: MedlinePlus