Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury
Pantaleão, Lucas C.; Loche, Elena; Fernandez-Twinn, Denise S.; Dearden, Laura; Córdova-Casanova, Adriana; Osmond, Clive; Salonen, Minna K.; Kajantie, Eero; Niu, Youguo; de Almeida-Faria, Juliana; Thackray, Benjamin D.; Mikkola, Tuija M.; Giussani, Dino A.; Murray, Andrew J.; Bushell, Martin; Eriksson, Johan G.; Ozanne, Susan E. (2024-01-22)
Elsevier
22.01.2024
Lucas C. Pantaleão, Elena Loche, Denise S. Fernandez-Twinn, Laura Dearden, Adriana Córdova-Casanova, Clive Osmond, Minna K. Salonen, Eero Kajantie, Youguo Niu, Juliana de Almeida-Faria, Benjamin D. Thackray, Tuija M. Mikkola, Dino A. Giussani, Andrew J. Murray, Martin Bushell, Johan G. Eriksson, Susan E. Ozanne, Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury, Molecular Metabolism, Volume 80, 2024, 101875, ISSN 2212-8778, https://doi.org/10.1016/j.molmet.2024.101875
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202402081642
https://urn.fi/URN:NBN:fi:oulu-202402081642
Tiivistelmä
Abstract
Objective:
We investigated the potential involvement of miRNAs in the developmental programming of cardiovascular diseases (CVD) by maternal obesity.
Methods:
Serum miRNAs were measured in individuals from the Helsinki Birth Cohort (with known maternal body mass index), and a mouse model was used to determine causative effects of maternal obesity during pregnancy and ischemia-reperfusion on offspring cardiac miRNA expression and release.
Results:
miR-15b-5p levels were increased in the sera of males born to mothers with higher BMI and in the hearts of adult mice born to obese dams. In an ex-vivo model of perfused mouse hearts, we demonstrated that cardiac tissue releases miR-15b-5p, and that some of the released miR-15b-5p was contained within small extracellular vesicles (EVs). We also demonstrated that release was higher from hearts exposed to maternal obesity following ischaemia/reperfusion. Over-expression of miR-15b-5p in vitro led to loss of outer mitochondrial membrane stability and to repressed fatty acid oxidation in cardiomyocytes.
Conclusions:
These findings suggest that miR-15-b could play a mechanistic role in the dysregulation of cardiac metabolism following exposure to an in utero obesogenic environment and that its release in cardiac EVs following ischaemic damage may be a novel factor contributing to inter-organ communication between the programmed heart and peripheral tissues.
Objective:
We investigated the potential involvement of miRNAs in the developmental programming of cardiovascular diseases (CVD) by maternal obesity.
Methods:
Serum miRNAs were measured in individuals from the Helsinki Birth Cohort (with known maternal body mass index), and a mouse model was used to determine causative effects of maternal obesity during pregnancy and ischemia-reperfusion on offspring cardiac miRNA expression and release.
Results:
miR-15b-5p levels were increased in the sera of males born to mothers with higher BMI and in the hearts of adult mice born to obese dams. In an ex-vivo model of perfused mouse hearts, we demonstrated that cardiac tissue releases miR-15b-5p, and that some of the released miR-15b-5p was contained within small extracellular vesicles (EVs). We also demonstrated that release was higher from hearts exposed to maternal obesity following ischaemia/reperfusion. Over-expression of miR-15b-5p in vitro led to loss of outer mitochondrial membrane stability and to repressed fatty acid oxidation in cardiomyocytes.
Conclusions:
These findings suggest that miR-15-b could play a mechanistic role in the dysregulation of cardiac metabolism following exposure to an in utero obesogenic environment and that its release in cardiac EVs following ischaemic damage may be a novel factor contributing to inter-organ communication between the programmed heart and peripheral tissues.
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- Avoin saatavuus [38358]
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