Journal article

Gene delivery of medium chain acyl-coenzyme A dehydrogenase induces physiological cardiac hypertrophy and protects against pathological remodelling

BC Bernardo, KL Weeks, T Pongsukwechkul, X Gao, H Kiriazis, N Cemerlang, EJH Boey, YK Tham, CJ Johnson, H Qian, XJ Du, P Gregorevic, JR McMullen

Clinical Science | PORTLAND PRESS LTD | Published : 2018

Abstract

We previously showed that medium chain acyl-coenzyme A dehydrogenase (MCAD, key regulator of fatty acid oxidation) is positively modulated in the heart by the cardioprotective kinase, phosphoinositide 3-kinase (PI3K(p110a)). Disturbances in cardiac metabolism are a feature of heart failure (HF) patients and targetingmetabolic defects is considered a potential therapeutic approach. The specific role of MCAD in the adult heart is unknown. To examine the role of MCAD in the heart and to assess the therapeutic potential of increasing MCAD in the failing heart, we developed a gene therapy tool using recombinant adeno-associated viral vectors (rAAV) encoding MCAD.We hypothesised that increasing MC..

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Grants

Awarded by Baker Foundation


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council Project Grant [grant number APP1009025 (to J.R.M)]; in part by the Victorian Government's Operational Infrastructure Support Program; the National Health and Medical Research Council Senior Research Fellowship [grant numbers 1043026, 1117835, 586604, 1078985 (to X.J.D., P.G., J.R.M.)]; the Australian Research Council Future Fellowship [grant number FT0001657 (to J.R.M.)]; the Alice Baker and Eleanor Shaw Fellowship (The Baker Foundation, Melbourne, Australiato B.C.B.); and the Australian Postgraduate Award and a National Heart Foundation Overseas Training Fellowship [grant number O12M6802 (to K.L.W.)].