The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart

Mitchel Tate; Gavin Higgins; Miles J. De Blasio; Runa  Lindblom; Darnel Prakoso; Minh Deo; Helen Kiriazis; Min Park; Carlos D.  Baeza-Garz; Stuart T.  Caldwell; Richard C.  Hartley; Thomas Krieg; Michael P Murphy; Melinda Coughlan; Rebecca H Ritchie

doi:10.1007/s10557-019-06914-9

The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart

Mitchel Tate, Gavin Higgins, Miles J. De Blasio, Runa Lindblom, Darnel Prakoso, Minh Deo, Helen Kiriazis, Min Park, Carlos D. Baeza-Garz, Stuart T. Caldwell, Richard C. Hartley, Thomas Krieg, Michael P Murphy, Melinda Coughlan, Rebecca H Ritchie

Diabetes

Research output: Contribution to journal › Article › Research › peer-review

15 Citations (Scopus)

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.

Original language	English
Pages (from-to)	669-674
Number of pages	6
Journal	Cardiovascular Drugs and Therapy
Volume	33
Issue number	6
DOIs	https://doi.org/10.1007/s10557-019-06914-9
Publication status	Published - Dec 2019

Keywords

Diabetes
Diabetic cardiomyopathy
Heart
Methylglyoxal

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10557-019-06914-9

289323234-oaFinal published version, 443 KB

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Tate, M., Higgins, G., De Blasio, M. J., Lindblom, R., Prakoso, D., Deo, M., Kiriazis, H., Park, M., Baeza-Garz, C. D., Caldwell, S. T., Hartley, R. C., Krieg, T., Murphy, M. P., Coughlan, M., & Ritchie, R. H. (2019). The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart. Cardiovascular Drugs and Therapy, 33(6), 669-674. https://doi.org/10.1007/s10557-019-06914-9

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title = "The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart",

abstract = "PurposeMethylglyoxal, 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.MethodsMale 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.ResultsAkita 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.ConclusionsOur 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.",

keywords = "Diabetes, Diabetic cardiomyopathy, Heart, Methylglyoxal",

author = "Mitchel Tate and Gavin Higgins and {De Blasio}, {Miles J.} and Runa Lindblom and Darnel Prakoso and Minh Deo and Helen Kiriazis and Min Park and Baeza-Garz, {Carlos D.} and Caldwell, {Stuart T.} and Hartley, {Richard C.} and Thomas Krieg and Murphy, {Michael P} and Melinda Coughlan and Ritchie, {Rebecca H}",

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doi = "10.1007/s10557-019-06914-9",

language = "English",

volume = "33",

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Tate, M, Higgins, G, De Blasio, MJ, Lindblom, R, Prakoso, D, Deo, M, Kiriazis, H, Park, M, Baeza-Garz, CD, Caldwell, ST, Hartley, RC, Krieg, T, Murphy, MP, Coughlan, M & Ritchie, RH 2019, 'The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart', Cardiovascular Drugs and Therapy, vol. 33, no. 6, pp. 669-674. https://doi.org/10.1007/s10557-019-06914-9

TY - JOUR

T1 - The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart

AU - Tate, Mitchel

AU - Higgins, Gavin

AU - De Blasio, Miles J.

AU - Lindblom, Runa

AU - Prakoso, Darnel

AU - Deo, Minh

AU - Kiriazis, Helen

AU - Park, Min

AU - Baeza-Garz, Carlos D.

AU - Caldwell, Stuart T.

AU - Hartley, Richard C.

AU - Krieg, Thomas

AU - Murphy, Michael P

AU - Coughlan, Melinda

AU - Ritchie, Rebecca H

PY - 2019/12

Y1 - 2019/12

N2 - PurposeMethylglyoxal, 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.MethodsMale 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.ResultsAkita 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.ConclusionsOur 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.

AB - PurposeMethylglyoxal, 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.MethodsMale 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.ResultsAkita 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.ConclusionsOur 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.

KW - Diabetes

KW - Diabetic cardiomyopathy

KW - Heart

KW - Methylglyoxal

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U2 - 10.1007/s10557-019-06914-9

DO - 10.1007/s10557-019-06914-9

M3 - Article

C2 - 31654171

AN - SCOPUS:85074434308

SN - 0920-3206

VL - 33

SP - 669

EP - 674

JO - Cardiovascular Drugs and Therapy

JF - Cardiovascular Drugs and Therapy

IS - 6

ER -

The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart

Abstract

Keywords

UN SDGs

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Correction to: The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart (Cardiovascular Drugs and Therapy, (2019), 33, 6, (669-674), 10.1007/s10557-019-06914-9)

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