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

Research output: Contribution to journalArticleResearchpeer-review

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 languageEnglish
Number of pages6
JournalCardiovascular Drugs and Therapy
DOIs
Publication statusAccepted/In press - 25 Oct 2019

Cite this

Tate, Mitchel ; Higgins, Gavin ; De Blasio, Miles J. ; Lindblom, Runa ; Prakoso, Darnel ; Deo, Minh ; Kiriazis, Helen ; Park, Min ; Baeza-Garz, Carlos D. ; Caldwell, Stuart T. ; Hartley, Richard C. ; Krieg, Thomas ; Murphy, Michael P ; Coughlan, Melinda. / The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart. In: Cardiovascular Drugs and Therapy. 2019.
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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.",
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",
year = "2019",
month = "10",
day = "25",
doi = "10.1007/s10557-019-06914-9",
language = "English",
journal = "Cardiovascular Drugs and Therapy",
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The Mitochondria-Targeted Methylglyoxal Sequestering Compound, MitoGamide, Is Cardioprotective in the Diabetic Heart. / Tate, Mitchel; Higgins, Gavin; De Blasio, Miles J.; Lindblom, Runa ; Prakoso, Darnel; Deo, Minh; Kiriazis, Helen; Park, Min; Baeza-Garz, Carlos D. ; Caldwell, Stuart T. ; Hartley, Richard C. ; Krieg, Thomas; Murphy, Michael P; Coughlan, Melinda.

In: Cardiovascular Drugs and Therapy, 25.10.2019.

Research output: Contribution to journalArticleResearchpeer-review

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

PY - 2019/10/25

Y1 - 2019/10/25

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.

U2 - 10.1007/s10557-019-06914-9

DO - 10.1007/s10557-019-06914-9

M3 - Article

JO - Cardiovascular Drugs and Therapy

JF - Cardiovascular Drugs and Therapy

SN - 0920-3206

ER -