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MEF2 transcriptional activity maintains mitochondrial adaptation in cardiac pressure overload

Item Type:Article
Title:MEF2 transcriptional activity maintains mitochondrial adaptation in cardiac pressure overload
Creators Name:el Azzouzi, H., van Oort, R.J., van der Nagel, R., Sluiter, W., Bergmann, M.W. and De Windt, L.J.
Abstract:AIMS: The transcription factor MEF2 is a downstream target for several hypertrophic signalling pathways in the heart, suggesting that MEF2 may act as a valuable therapeutic target in the treatment of heart failure. METHODS AND RESULTS: In this study, we investigated the potential benefits of overall MEF2 inhibition in a mouse model of chronic pressure overloading, by subjecting transgenic mice expressing a dominant negative form of MEF2 (DN-MEF2 Tg) in the heart, to transverse aortic constriction (TAC). Histological analysis revealed no major differences in cardiac remodelling between DN-MEF2 Tg and control mice after TAC. Surprisingly, echocardiographic analysis revealed that DN-MEF2 Tg mice had a decrease in cardiac function compared with control animals. Analysis of the mitochondrial respiratory chain showed that DN-MEF2 Tg mice displayed lower expression of NADH dehydrogenase subunit 6 (ND6), part of mitochondrial Complex I. The reduced expression of ND6 in DN-MEF2 Tg mice after pressure overload correlated with an increase in cell death secondary to overproduction of reactive oxygen species (ROS). CONCLUSION: Our data suggest that MEF2 transcriptional activity is required for mitochondrial function and its inhibition predisposes the heart to impaired mitochondrial function, overproduction of ROS, enhanced cell death, and cardiac dysfunction, following pressure overload.
Keywords:MEF2, NADH Dehydrogenase Subunit 6, Transverse Aortic Constriction, Mitochondria, Heart Failure, Reactive Oxygen Species, Animals, Mice
Source:European Journal of Heart Failure
ISSN:1388-9842
Publisher:Oxford University Press
Volume:12
Number:1
Page Range:4-12
Date:January 2010
Official Publication:https://doi.org/10.1093/eurjhf/hfp165
PubMed:View item in PubMed

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