Programming of cardiac metabolism by miR-15b-5p, a miRNA released in cardiac extracellular vesicles following ischemia-reperfusion injury.

Autor:	Pantaleão LC; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Loche E; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Fernandez-Twinn DS; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Dearden L; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Córdova-Casanova A; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Osmond C; MRC Lifecourse Epidemiology Unit, University of Southampton, UK., Salonen MK; Finnish Institute for Health and Welfare, Public Health Unit, Finland., Kajantie E; Finnish Institute for Health and Welfare, Public Health Unit, Finland; Clinical Medicine Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Niu Y; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK., de Almeida-Faria J; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK., Thackray BD; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK., Mikkola TM; Finnish Institute for Health and Welfare, Public Health Unit, Finland; Folkhalsan Research Center, Helsinki, Finland; Faculty of Medicine, University of Helsinki, Finland., Giussani DA; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK., Murray AJ; Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UK., Bushell M; CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK., Eriksson JG; Folkhalsan Research Center, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Finland; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Ozanne SE; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge, UK. Electronic address: seo10@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2024 Feb; Vol. 80, pp. 101875. Date of Electronic Publication: 2024 Jan 11.
DOI:	10.1016/j.molmet.2024.101875
Abstrakt:	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. Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists. (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze:	MEDLINE
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