Imperial College London
Alternate

ProfessorNadiaRosenthal

Faculty of Medicine, National Heart & Lung Institute

Chair in Cardiovascular Science&ScientificDirector
 
 
 
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Contact

 

+44 (0)20 7594 2737n.rosenthal

 
 
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Location

 

424W2ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wilmanns:2019:10.1016/j.molmet.2018.11.002,
author = {Wilmanns, JC and Pandey, R and Hon, O and Chandran, A and Schilling, JM and Forte, E and Wu, Q and Cagnone, G and Bais, P and Philip, V and Coleman, D and Kocalis, H and Archer, SK and Pearson, JT and Ramialison, M and Heineke, J and Patel, HH and Rosenthal, NA and Furtado, MB and Costa, MW},
doi = {10.1016/j.molmet.2018.11.002},
journal = {Molecular Metabolism},
pages = {102--114},
title = {Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease},
url = {http://dx.doi.org/10.1016/j.molmet.2018.11.002},
volume = {20},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OBJECTIVE: Congenital heart disease (CHD) is the most frequent birth defect worldwide. The number of adult patients with CHD, now referred to as ACHD, is increasing with improved surgical and treatment interventions. However the mechanisms whereby ACHD predisposes patients to heart dysfunction are still unclear. ACHD is strongly associated with metabolic syndrome, but how ACHD interacts with poor modern lifestyle choices and other comorbidities, such as hypertension, obesity, and diabetes, is mostly unknown. METHODS: We used a newly characterized mouse genetic model of ACHD to investigate the consequences and the mechanisms associated with combined obesity and ACHD predisposition. Metformin intervention was used to further evaluate potential therapeutic amelioration of cardiac dysfunction in this model. RESULTS: ACHD mice placed under metabolic stress (high fat diet) displayed decreased left ventricular ejection fraction. Comprehensive physiological, biochemical, and molecular analysis showed that ACHD hearts exhibited early changes in energy metabolism with increased glucose dependence as main cardiac energy source. These changes preceded cardiac dysfunction mediated by exposure to high fat diet and were associated with increased disease severity. Restoration of metabolic balance by metformin administration prevented the development of heart dysfunction in ACHD predisposed mice. CONCLUSIONS: This study reveals that early metabolic impairment reinforces heart dysfunction in ACHD predisposed individuals and diet or pharmacological interventions can be used to modulate heart function and attenuate heart failure. Our study suggests that interactions between genetic and metabolic disturbances ultimately lead to the clinical presentation of heart failure in patients with ACHD. Early manipulation of energy metabolism may be an important avenue for intervention in ACHD patients to prevent or delay onset of heart failure and secondary comorbidities. These interactions raise
AU  - Wilmanns,JC
AU  - Pandey,R
AU  - Hon,O
AU  - Chandran,A
AU  - Schilling,JM
AU  - Forte,E
AU  - Wu,Q
AU  - Cagnone,G
AU  - Bais,P
AU  - Philip,V
AU  - Coleman,D
AU  - Kocalis,H
AU  - Archer,SK
AU  - Pearson,JT
AU  - Ramialison,M
AU  - Heineke,J
AU  - Patel,HH
AU  - Rosenthal,NA
AU  - Furtado,MB
AU  - Costa,MW
DO  - 10.1016/j.molmet.2018.11.002
EP  - 114
PY  - 2019///
SN  - 2212-8778
SP  - 102
TI  - Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2018.11.002
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30482476
UR  - http://hdl.handle.net/10044/1/66333
VL  - 20
ER  -
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