Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus

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Abstract

Diabetes mellitus (DM) is a progressive, chronic metabolic disorder characterized by high oxidative stress, which can lead to cardiac damage. Methionine sulfoxylation (MetO) of proteins by excessive reactive oxygen species (ROS) can impair the basic functionality of essential cellular proteins, contributing to heart failure. Methionine sulfoxide reductase B2 (MsrB2) can reverse oxidation induced MetO in mitochondrial proteins, so we investigated its role in diabetic cardiomyopathy. We observed that DM-induced heart damage in diabetic mice model is characterized by increased ROS, increased protein MetO with mitochondria structural pathology, and cardiac fibrosis. In addition, MsrB2 was significantly increased in mouse DM cardiomyocytes, supporting the induction of a protective process. Further, MsrB2 directly induces Parkin and LC3 activation (mitophagy markers) in cardiomyocytes. In MsrB2, knockout mice displayed abnormal electrophysiological function, as determined by ECG analysis. Histological analysis confirmed increased cardiac fibrosis and disrupted cardiac tissue in MsrB2 knockout DM mice. We then corroborated our findings in human DM heart samples. Our study demonstrates that increased MsrB2 expression in the heart protects against diabetic cardiomyopathy.

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The online version contains supplementary material available at 10.1186/s13098-024-01390-0.

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Most cited references 45

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Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association

Salim S. Virani, Alvaro Alonso, Hugo Aparicio … (2021)

The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

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Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States

Ronald CW Ma, Juliana Chan (2013)

There is an epidemic of diabetes in Asia. Type 2 diabetes develops in East Asian patients at a lower mean body mass index (BMI) compared with those of European descent. At any given BMI, East Asians have a greater amount of body fat and a tendency to visceral adiposity. In Asian patients, diabetes develops at a younger age and is characterized by early β cell dysfunction in the setting of insulin resistance, with many requiring early insulin treatment. The increasing proportion of young-onset and childhood type 2 diabetes is posing a particular threat, with these patients being at increased risk of developing diabetic complications. East Asian patients with type 2 diabetes have a higher risk of developing renal complications than Europeans and, with regard to cardiovascular complications, a predisposition for developing strokes. In addition to cardiovascular–renal disease, cancer is emerging as the other main cause of mortality. While more research is needed to explain these interethnic differences, urgent and concerted actions are needed to raise awareness, facilitate early diagnosis, and encourage preventive strategies to combat these growing disease burdens.

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Mitochondrial dynamics, mitophagy and cardiovascular disease.

César Vasquez-Trincado, Ivonne García-Carvajal, Christian Pennanen … (2016)

Cardiac hypertrophy is often initiated as an adaptive response to haemodynamic stress or myocardial injury, and allows the heart to meet an increased demand for oxygen. Although initially beneficial, hypertrophy can ultimately contribute to the progression of cardiac disease, leading to an increase in interstitial fibrosis and a decrease in ventricular function. Metabolic changes have emerged as key mechanisms involved in the development and progression of pathological remodelling. As the myocardium is a highly oxidative tissue, mitochondria play a central role in maintaining optimal performance of the heart. 'Mitochondrial dynamics', the processes of mitochondrial fusion, fission, biogenesis and mitophagy that determine mitochondrial morphology, quality and abundance have recently been implicated in cardiovascular disease. Studies link mitochondrial dynamics to the balance between energy demand and nutrient supply, suggesting that changes in mitochondrial morphology may act as a mechanism for bioenergetic adaptation during cardiac pathological remodelling. Another critical function of mitochondrial dynamics is the removal of damaged and dysfunctional mitochondria through mitophagy, which is dependent on the fission/fusion cycle. In this article, we discuss the latest findings regarding the impact of mitochondrial dynamics and mitophagy on the development and progression of cardiovascular pathologies, including diabetic cardiomyopathy, atherosclerosis, damage from ischaemia-reperfusion, cardiac hypertrophy and decompensated heart failure. We will address the ability of mitochondrial fusion and fission to impact all cell types within the myocardium, including cardiac myocytes, cardiac fibroblasts and vascular smooth muscle cells. Finally, we will discuss how these findings can be applied to improve the treatment and prevention of cardiovascular diseases.

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Author and article information

Contributors

Seung Hee Lee: Seungheelee@korea.kr

John Hwa: john.hwa@yale.edu

Won-Ho Kim: jhkwh@korea.kr

Journal

Journal ID (nlm-ta): Diabetol Metab Syndr

Journal ID (iso-abbrev): Diabetol Metab Syndr

Title: Diabetology & Metabolic Syndrome

Publisher: BioMed Central (London )

ISSN (Electronic): 1758-5996

Publication date (Electronic): 5 July 2024

Publication date PMC-release: 5 July 2024

Publication date Collection: 2024

Volume: 16

Electronic Location Identifier: 149

Affiliations

[1 ]Division of Cardiovascular Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health, ( https://ror.org/00qdsfq65) Cheongju, Republic of Korea

[2 ]Division of Endocrine and Kidney Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health, ( https://ror.org/00qdsfq65) Cheongju, Republic of Korea

[3 ]Division of Research Support, Department of Research Planning and Coordination, Korea National Institute of Health, ( https://ror.org/00qdsfq65) Cheongju, Republic of Korea

[4 ]Yale Cardiovascular Research Center, New Haven, USA

Article

Publisher ID: 1390

DOI: 10.1186/s13098-024-01390-0

PMC ID: 11225187

PubMed ID: 38970135

SO-VID: 3458c7ab-a05a-4051-97d0-b1b693191a06

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 11 April 2024

Date accepted : 25 June 2024

Funding

Funded by: Korea National Institute of Health intramural research grant

Award ID: 2018-NI007-02

Award ID: 2021-NI023-02

Award ID: 2018-NI007-02

Award ID: 2021-NI023-02

Award ID: 2018-NI007-02

Funded by: National Institute of Health

Award ID: RO1HL122815, RO1HL150515

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ScienceOpen disciplines: Nutrition & Dietetics

Keywords: msrb2,diabetes,cardiac complications,mitophagy

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ScienceOpen disciplines: Nutrition & Dietetics

Keywords: msrb2, diabetes, cardiac complications, mitophagy

Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus

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Most cited references 45

Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association

Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States

Mitochondrial dynamics, mitophagy and cardiovascular disease.

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