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Antioxidants
Special Issues
Oxidative Stress in Metabolic Cardiomyopathy
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Oxidative Stress in Metabolic Cardiomyopathy

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 14168

Special Issue Editor

Dr. Mariana G. Rosca

E-Mail Website
Guest Editor
College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USA
Interests: mitochondrial disease; redox state; oxidative stress; diabetes; heart

Special Issue Information

Dear Colleagues, 

Metabolic cardiomyopathy is a specific type of cardiac muscle disease associated with metabolic syndrome and diabetes which is not causally related to the common morbidity risks factors induced by metabolic challenges, including coronary artery disease and hypertension. This clinical condition has been described in both human and animal subjects. This pathological condition is initially characterized by cardiac interstitial fibrosis, leading to a restrictive functional phenotype with decreased left ventricle early diastolic filling and increased end-diastolic pressure with preserved left ventricle ejection fraction. The disease progresses to cardiac remodelling and left ventricular hypertrophy, with reduced cardiac compliance that coincides with reduced ejection fraction. Metabolic cardiomyopathy doubles the risk of congestive heart failure. The initiation and progression to congestive heart failure are multifactorial. Underlying pathogenic mechanisms include systemic and cardiac insulin resistance and inflammation, increased energetic substrates (glucose, free fatty acids), the activation of endocrine signalling pathways such as renin angiotensin aldosterone and sympathetic nervous systems, and alterations in contractile apparatus and calcium handling. These mechanisms are either the cause or the effect of oxidative stress, which may be the major executioner of cardiac damage.

We invite all colleagues to submit the results of their research or literature review to this Special Issue, which has the goal of bringing together the most recent findings on the sources and downstream effects of oxidative stress in metabolic heart disease. We appreciate submissions regarding the difference between the role of increased oxidative stress in the initiation and progression of diabetic cardiomyopathy in human subjects versus animal models, as well as in male versus female subjects. We also welcome reports regarding various sources of oxidative stress, including mitochondria, NADPH oxidase, xanthine oxidase, microsomal P-450 enzyme, and uncoupled NO synthase. We hope that this Special Issue on Oxidative Stress in Metabolic Cardiomyopathy will compile the most recent discoveries and reveal novel and targeted antioxidant therapeutic approaches.

We look forward to your participation.  

Dr. Mariana G. Rosca
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Diabetes
  • Metabolic syndrome
  • Heart
  • Oxidative stress
  • Mitochondria
  • NADPH oxidase
  • Xanthine oxidase
  • Microsomal P-450 enzyme
  • Uncoupled NO synthase
  • Gender disparity

Published Papers (4 papers)

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Research

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14 pages, 4257 KiB  
Article
Hyperkalemic or Low Potassium Cardioplegia Protects against Reduction of Energy Metabolism by Oxidative Stress
by Hongting Diao, Haiwei Gu and Qin M. Chen
Antioxidants 2023, 12(2), 452; https://doi.org/10.3390/antiox12020452 - 10 Feb 2023
Cited by 1 | Viewed by 2174
Abstract
Open-heart surgery is often an unavoidable option for the treatment of cardiovascular disease and prevention of cardiomyopathy. Cardiopulmonary bypass surgery requires manipulating cardiac contractile function via the perfusion of a cardioplegic solution. Procedure-associated ischemia and reperfusion (I/R) injury, a major source of oxidative [...] Read more.
Open-heart surgery is often an unavoidable option for the treatment of cardiovascular disease and prevention of cardiomyopathy. Cardiopulmonary bypass surgery requires manipulating cardiac contractile function via the perfusion of a cardioplegic solution. Procedure-associated ischemia and reperfusion (I/R) injury, a major source of oxidative stress, affects postoperative cardiac performance and long-term outcomes. Using large-scale liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based metabolomics, we addressed whether cardioplegic solutions affect the baseline cellular metabolism and prevent metabolic reprogramming by oxidative stress. AC16 cardiomyocytes in culture were treated with commonly used cardioplegic solutions, High K+ (HK), Low K+ (LK), Del Nido (DN), histidine–tryptophan–ketoglutarate (HTK), or Celsior (CS). The overall metabolic profile shown by the principal component analysis (PCA) and heatmap revealed that HK or LK had a minimal impact on the baseline 78 metabolites, whereas HTK or CS significantly repressed the levels of multiple amino acids and sugars. H2O2-induced sublethal mild oxidative stress causes decreases in NAD, nicotinamide, or acetylcarnitine, but increases in glucose derivatives, including glucose 6-P, glucose 1-P, fructose, mannose, and mannose 6-P. Additional increases include metabolites of the pentose phosphate pathway, D-ribose-5-P, L-arabitol, adonitol, and xylitol. Pretreatment with HK or LK cardioplegic solution prevented most metabolic changes and increases of reactive oxygen species (ROS) elicited by H2O2. Our data indicate that HK and LK cardioplegic solutions preserve baseline metabolism and protect against metabolic reprogramming by oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress in Metabolic Cardiomyopathy)
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17 pages, 7382 KiB  
Article
Supplementation with a Cocoa–Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats
by Esther García-Díez, María Elvira López-Oliva, Alicia Caro-Vadillo, Francisco Pérez-Vizcaíno, Jara Pérez-Jiménez, Sonia Ramos and María Ángeles Martín
Antioxidants 2022, 11(2), 432; https://doi.org/10.3390/antiox11020432 - 21 Feb 2022
Cited by 12 | Viewed by 4007
Abstract
Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have [...] Read more.
Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa–carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM. Full article
(This article belongs to the Special Issue Oxidative Stress in Metabolic Cardiomyopathy)
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Review

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12 pages, 353 KiB  
Review
Inhibition of Pyruvate Dehydrogenase in the Heart as an Initiating Event in the Development of Diabetic Cardiomyopathy
by Abdallah Elnwasany, Heba A. Ewida, Pamela A. Szweda and Luke I. Szweda
Antioxidants 2023, 12(3), 756; https://doi.org/10.3390/antiox12030756 - 20 Mar 2023
Cited by 2 | Viewed by 3543
Abstract
Obesity affects a growing fraction of the population and is a risk factor for type 2 diabetes and cardiovascular disease. Even in the absence of hypertension and coronary artery disease, type 2 diabetes can result in a heart disease termed diabetic cardiomyopathy. Diminished [...] Read more.
Obesity affects a growing fraction of the population and is a risk factor for type 2 diabetes and cardiovascular disease. Even in the absence of hypertension and coronary artery disease, type 2 diabetes can result in a heart disease termed diabetic cardiomyopathy. Diminished glucose oxidation, increased reliance on fatty acid oxidation for energy production, and oxidative stress are believed to play causal roles. However, the progression of metabolic changes and mechanisms by which these changes impact the heart have not been established. Cardiac pyruvate dehydrogenase (PDH), the central regulatory site for glucose oxidation, is rapidly inhibited in mice fed high dietary fat, a model of obesity and diabetes. Increased reliance on fatty acid oxidation for energy production, in turn, enhances mitochondrial pro-oxidant production. Inhibition of PDH may therefore initiate metabolic inflexibility and oxidative stress and precipitate diabetic cardiomyopathy. We discuss evidence from the literature that supports a role for PDH inhibition in loss in energy homeostasis and diastolic function in obese and diabetic humans and in rodent models. Finally, seemingly contradictory findings highlight the complexity of the disease and the need to delineate progressive changes in cardiac metabolism, the impact on myocardial structure and function, and the ability to intercede. Full article
(This article belongs to the Special Issue Oxidative Stress in Metabolic Cardiomyopathy)
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17 pages, 896 KiB  
Review
The Importance of SGLT-2 Inhibitors as Both the Prevention and the Treatment of Diabetic Cardiomyopathy
by Klaudia Kowalska, Piotr Wilczopolski, Dominika Buławska, Ewelina Młynarska, Jacek Rysz and Beata Franczyk
Antioxidants 2022, 11(12), 2500; https://doi.org/10.3390/antiox11122500 - 19 Dec 2022
Cited by 4 | Viewed by 2784
Abstract
According to the 2021 report of the International Diabetes Federation (IDF), there have been approximately 573 million cases of type 2 diabetes mellitus (T2DM) among adults, which sets the disease as a major concern in healthcare worldwide. The development of T2DM is strongly [...] Read more.
According to the 2021 report of the International Diabetes Federation (IDF), there have been approximately 573 million cases of type 2 diabetes mellitus (T2DM) among adults, which sets the disease as a major concern in healthcare worldwide. The development of T2DM is strongly promoted by unhealthy lifestyle factors associated with urbanization and western civilization. The disease is associated with a broad list of systemic complications that can result in premature death, disability and significantly reduced quality of life. The most dramatic in their consequences are cardiovascular complications of T2DM. Our work focuses on one such complication that is specific for diabetes, named diabetic cardiomyopathy (DC). In this condition cardiac dysfunction occurs despite the absence of underlying hypertension, coronary artery disease and valvular disease, which suggest a leading role for metabolic disturbances as a cause. We aimed to establish the role of relatively new hypoglycaemic drugs that have taken the medical world by storm with their broad pleiotropic effects—SGLT-2 inhibitors—in the prevention and treatment of DC at any stage. Full article
(This article belongs to the Special Issue Oxidative Stress in Metabolic Cardiomyopathy)
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