A gene therapy targeting medium-chain acyl-CoA dehydrogenase (MCAD) did not protect against diabetes-induced cardiac pathology

Kate L Weeks; Helen Kiriazis; Glenn D Wadley; Emma I Masterman; Nicola M Sergienko; Antonia JA Raaijmakers; Adam J Trewin; Claudia A Harmawan; Gunes S Yildiz; Yingying Liu; Brian G Drew; Paul Gregorevic; Lea MD Delbridge; Julie R McMullen; Bianca C Bernardo

Journal article

A gene therapy targeting medium-chain acyl-CoA dehydrogenase (MCAD) did not protect against diabetes-induced cardiac pathology

Kate L Weeks, Helen Kiriazis, Glenn D Wadley, Emma I Masterman, Nicola M Sergienko, Antonia JA Raaijmakers, Adam J Trewin, Claudia A Harmawan, Gunes S Yildiz, Yingying Liu, Brian G Drew, Paul Gregorevic, Lea MD Delbridge, Julie R McMullen, Bianca C Bernardo

Journal of Molecular Medicine | Springer | Published : 2024

DOI: 10.1007/s00109-023-02397-2

Abstract

Diabetic cardiomyopathy describes heart disease in patients with diabetes who have no other cardiac conditions but have a higher risk of developing heart failure. Specific therapies to treat the diabetic heart are limited. A key mechanism involved in the progression of diabetic cardiomyopathy is dysregulation of cardiac energy metabolism. The aim of this study was to determine if increasing the expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD; encoded by Acadm), a key regulator of fatty acid oxidation, could improve the function of the diabetic heart. Male mice were administered streptozotocin to induce diabetes, which led to diastolic dysfunction 8 weeks post-injection. Mice t..

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University of Melbourne Researchers

Kate Weeks Author

Hanneke Raaijmakers Author

Brian Drew Author

Paul Gregorevic Author

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Funding Acknowledgements

We wish to thank Ms Stephanie Jansen (Alfred Research Alliance Animal Facility) for performing the AAV tail vein injections, Ms Amy Hsu (Baker Heart and Diabetes Institute) for technical assistance, and Dr Hongwei Qian (University of Melbourne) for producing the AAV vectors.