Evidence map›Paper›PMID 37987775›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2024

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 J A Raaijmakers, Adam J Trewin, Claudia A Harmawan, Gunes S Yildiz, Yingying Liu and 5 more

Abstract read
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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
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  7. Challenges and Future Prospectives in Circular RNA Investigation.Advances in experimental medicine and biology · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Kate L WeeksDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
Helen KiriazisDepartment of Cardiometabolic Health, University of Melbourne, Parkville, VIC, 3010, Australia.
Glenn D WadleyInstitute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, 3125, Australia.
Emma I MastermanBaker Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia.
Nicola M SergienkoDepartment of Diabetes, Central Clinical School, Monash University, Clayton, VIC, 3800, Australia.
Antonia J A RaaijmakersDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
Adam J TrewinDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
Claudia A HarmawanBaker Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia.
Gunes S YildizBaker Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia.
Yingying LiuBaker Heart and Diabetes Institute, PO Box 6492, Melbourne, VIC, 3004, Australia.
Brian G DrewDepartment of Cardiometabolic Health, University of Melbourne, Parkville, VIC, 3010, Australia.
Paul GregorevicDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
Lea M D DelbridgeDepartment of Anatomy and Physiology, University of Melbourne, Parkville, VIC, 3010, Australia.
Julie R McMullenDepartment of Cardiometabolic Health, University of Melbourne, Parkville, VIC, 3010, Australia.
Bianca C BernardoDepartment of Diabetes, Central Clinical School, Monash University, Clayton, VIC, 3800, Australia. bianca.bernardo@baker.edu.au.ORCID 0000-0002-4534-0549
Baker Heart and Diabetes Institute · AUThe University of Melbourne · AUDeakin University · AU

Funding

Baker Heart and Diabetes Institute Baker FellowshipBaker Heart and Diabetes Institute Women in Science GrantDiabetes Australia Y19G-BERBMonash University Research Training Program scholarshipNational Health and Medical Research Council 1078985National Health and Medical Research Council 1117835National Health and Medical Research Council 2017070National Heart Foundation of Australia 102539 (Future Leader Fellowship)
6 · The paper itself

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 then received cardiac-selective adeno-associated viral vectors encoding MCAD (rAAV6:MCAD) or control AAV and were followed for 8 weeks. In the non-diabetic heart, rAAV6:MCAD increased MCAD expression (mRNA and protein) and increased Acadl and Acadvl, but an increase in MCAD enzyme activity was not detectable. rAAV6:MCAD delivery in the diabetic heart increased MCAD mRNA expression but did not significantly increase protein, activity, or improve diabetes-induced cardiac pathology or molecular metabolic and lipid markers. The uptake of AAV viral vectors was reduced in the diabetic versus non-diabetic heart, which may have implications for the translation of AAV therapies into the clinic. KEY MESSAGES: The effects of increasing MCAD in the diabetic heart are unknown. Delivery of rAAV6:MCAD increased MCAD mRNA and protein, but not enzyme activity, in the non-diabetic heart. Independent of MCAD enzyme activity, rAAV6:MCAD increased Acadl and Acadvl in the non-diabetic heart. Increasing MCAD cardiac gene expression alone was not sufficient to protect against diabetes-induced cardiac pathology. AAV transduction efficiency was reduced in the diabetic heart, which has clinical implications.

Indexed as

Congenital Bone Marrow Failure SyndromesDiabetes MellitusDiabetic CardiomyopathiesLipid Metabolism, Inborn ErrorsMitochondrial DiseasesMuscular DiseasesAcyl-CoA DehydrogenaseAnimalsGenetic TherapyHumansMaleMiceRNA, MessengerAcyl-CoA DehydrogenaseRNA, MessengerDehydrogenaseDiabetesDiabetic cardiomyopathyGene therapyMetabolism

Identifiers

PMID37987775
OpenAlexW4388851316

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.