The mitochondria-targeted methylglyoxal sequestering compound, MitoGamide, is cardioprotective in the diabetic heart

Tate, M. et al. (2019) The mitochondria-targeted methylglyoxal sequestering compound, MitoGamide, is cardioprotective in the diabetic heart. Cardiovascular Drugs and Therapy, 33, pp. 669-674. (doi: 10.1007/s10557-019-06929-2) (PMID:31654171) (PMCID:PMC6994445)

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Abstract

PURPOSE: Methylglyoxal, a by-product of glycolysis and a precursor in the formation of advanced glycation end-products, is significantly elevated in the diabetic myocardium. Therefore, we sought to investigate the mitochondria-targeted methylglyoxal scavenger, MitoGamide, in an experimental model of spontaneous diabetic cardiomyopathy. METHODS: Male 6-week-old Akita or wild type mice received daily oral gavage of MitoGamide or vehicle for 10 weeks. Several morphological and systemic parameters were assessed, as well as cardiac function by echocardiography. RESULTS: Akita mice were smaller in size than wild type counterparts in terms of body weight and tibial length. Akita mice exhibited elevated blood glucose and glycated haemoglobin. Total heart and individual ventricles were all smaller in Akita mice. None of the aforementioned parameters was impacted by MitoGamide treatment. Echocardiographic analysis confirmed that cardiac dimensions were smaller in Akita hearts. Diastolic dysfunction was evident in Akita mice, and notably, MitoGamide treatment preferentially improved several of these markers, including e'/a' ratio and E/e' ratio. CONCLUSIONS: Our findings suggest that MitoGamide, a novel mitochondria-targeted approach, offers cardioprotection in experimental diabetes and therefore may offer therapeutic potential for the treatment of cardiomyopathy in patients with diabetes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Caldwell, Dr Stuart and Hartley, Professor Richard
Authors: Tate, M., Higgins, G. C., De Blasio, M. J., Lindblom, R., Prakoso, D., Deo, M., Kiriazis, H., Park, M., Barza-Garza, C. D., Caldwell, S. T., Hartley, R. C., Krieg, T., Murphy, M. P., Coughlan, M. T., and Ritchie, R. H.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Cardiovascular Drugs and Therapy
Publisher:Springer
ISSN:0920-3206
ISSN (Online):1573-7241
Published Online:25 October 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Cardiovascular Drugs and Therapy 33:669-674
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172617Exploring mitochondrial metabolism in health and disease using targeted biological chemistryRichard HartleyWellcome Trust (WELLCOTR)110158/Z/15/ZChemistry
165401Developing chemical mass spectrometry probes to assess the production of reactive oxygen species in vivoRichard HartleyBiotechnology and Biological Sciences Research Council (BBSRC)BB/I012826/1Chemistry