scholarly journals Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage

2014 ◽  
Vol 5 (6) ◽  
pp. 623-634 ◽  
Author(s):  
Quan Liu ◽  
Shudong Wang ◽  
Lu Cai
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy

Diabetic Cardiomyopathy and Oxidative Stress: Role of Antioxidants

2011 ◽  
Vol 9 (4) ◽  
pp. 225-230 ◽  
Author(s):  
Rajarajan A. Thandavarayan ◽  
Vijayasree V. Giridharan ◽  
Kenichi Watanabe ◽  
Tetsuya Konishi
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
And Oxidative Stress

scholarly journals The Role of Heme Oxygenase 1 in the Protective Effect of Caloric Restriction against Diabetic Cardiomyopathy

2019 ◽  
Vol 20 (10) ◽  
pp. 2427 ◽  
Author(s):  
Maayan Waldman ◽  
Vadim Nudelman ◽  
Asher Shainberg ◽  
Romy Zemel ◽  
Ran Kornwoski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Beneficial Effect ◽  
Heme Oxygenase ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Heme Oxygenase 1 ◽  
Ros Production ◽  
Diabetic Mice ◽  
Protein Levels

Type 2 diabetes mellitus (DM2) leads to cardiomyopathy characterized by cardiomyocyte hypertrophy, followed by mitochondrial dysfunction and interstitial fibrosis, all of which are exacerbated by angiotensin II (AT). SIRT1 and its transcriptional coactivator target PGC-1α (peroxisome proliferator-activated receptor-γ coactivator), and heme oxygenase-1 (HO-1) modulates mitochondrial biogenesis and antioxidant protection. We have previously shown the beneficial effect of caloric restriction (CR) on diabetic cardiomyopathy through intracellular signaling pathways involving the SIRT1–PGC-1α axis. In the current study, we examined the role of HO-1 in diabetic cardiomyopathy in mice subjected to CR. Methods: Cardiomyopathy was induced in obese diabetic (db/db) mice by AT infusion. Mice were either fed ad libitum or subjected to CR. In an in vitro study, the reactive oxygen species (ROS) level was determined in cardiomyocytes exposed to different glucose levels (7.5–33 mM). We examined the effects of Sn(tin)-mesoporphyrin (SnMP), which is an inhibitor of HO activity, the HO-1 inducer cobalt protoporphyrin (CoPP), and the SIRT1 inhibitor (EX-527) on diabetic cardiomyopathy. Results: Diabetic mice had low levels of HO-1 and elevated levels of the oxidative marker malondialdehyde (MDA). CR attenuated left ventricular hypertrophy (LVH), increased HO-1 levels, and decreased MDA levels. SnMP abolished the protective effects of CR and caused pronounced LVH and cardiac metabolic dysfunction represented by suppressed levels of adiponectin, SIRT1, PPARγ, PGC-1α, and increased MDA. High glucose (33 mM) increased ROS in cultured cardiomyocytes, while SnMP reduced SIRT1, PGC-1α levels, and HO activity. Similarly, SIRT1 inhibition led to a reduction in PGC-1α and HO-1 levels. CoPP increased HO-1 protein levels and activity, SIRT1, and PGC-1α levels, and decreased ROS production, suggesting a positive feedback between SIRT1 and HO-1. Conclusion: These results establish a link between SIRT1, PGC-1α, and HO-1 signaling that leads to the attenuation of ROS production and diabetic cardiomyopathy. CoPP mimicked the beneficial effect of CR, while SnMP increased oxidative stress, aggravating cardiac hypertrophy. The data suggest that increasing HO-1 levels constitutes a novel therapeutic approach to protect the diabetic heart. Brief Summary: CR attenuates cardiomyopathy, and increases HO-1, SIRT activity, and PGC-1α protein levels in diabetic mice. High glucose reduces adiponectin, SIRT1, PGC1-1α, and HO-1 levels in cardiomyocytes, resulting in oxidative stress. The pharmacological activation of HO-1 activity mimics the effect of CR, while SnMP increased oxidative stress and cardiac hypertrophy. These data suggest the critical role of HO-1 in protecting the diabetic heart.

Role of catecholamines in the pathogenesis of diabetic cardiomyopathy

2019 ◽  
Vol 97 (9) ◽  
pp. 815-819 ◽  
Author(s):  
Naranjan S. Dhalla ◽  
Pallab K. Ganguly ◽  
Sukhwinder K. Bhullar ◽  
Paramjit S. Tappia
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Oxidation Products ◽  
Sympathetic Nervous ◽  
Myocardial Gene Expression

Although the sympathetic nervous system plays an important role in the regulation of cardiac function, the overactivation of the sympathetic nervous system under stressful conditions including diabetes has been shown to result in the excessive production of circulating catecholamines as well as an increase in the myocardial concentration of catecholamines. In this brief review, we provide some evidence to suggest that the oxidation products of catecholamines such as aminochrome and oxyradicals, lead to metabolic derangements, Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+, as well as activation of proteases and changes in myocardial gene expression. These alterations due to elevated levels of circulatory catecholamines are associated with oxidative stress, subcellular remodeling, and the development of cardiac dysfunction in chronic diabetes.

scholarly journals Potential Role of Nuclear FactorκB in Diabetic Cardiomyopathy

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
O. Lorenzo ◽  
B. Picatoste ◽  
S. Ares-Carrasco ◽  
E. Ramírez ◽  
J. Egido ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Diabetic Cardiomyopathy ◽  
Nuclear Factor Kappa B ◽  
Potential Role ◽  
Heart Diseases ◽  
Cardiac Injury ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Diabetic cardiomyopathy entails the cardiac injury induced by diabetes independently of any vascular disease or hypertension. Some transcription factors have been proposed to control the gene program involved in the setting and development of related processes. Nuclear factor-kappa B is a pleiotropic transcription factor associated to the regulation of many heart diseases. However, the nuclear factor-kappa B role in diabetic cardiomyopathy is under investigation. In this paper, we review the nuclear factor-kappa B pathway and its role in several processes that have been linked to diabetic cardiomyopathy, such as oxidative stress, inflammation, endothelial dysfunction, fibrosis, hypertrophy and apoptosis.

scholarly journals The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis

2021 ◽  
Vol 22 (10) ◽  
pp. 5094
Author(s):  
Fatin Farhana Jubaidi ◽  
Satirah Zainalabidin ◽  
Izatus Shima Taib ◽  
Zariyantey Abd Hamid ◽  
Siti Balkis Budin
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Diabetic Cardiomyopathy ◽  
Mortality Risk ◽  
Potential Role ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Diabetic Patients ◽  
Remedial Actions

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.

Nampt Potentiates Antioxidant Defense in Diabetic Cardiomyopathy

2021 ◽  
Author(s):  
Shin-ichi Oka ◽  
Jaemin Byun ◽  
Chun-yang Huang ◽  
Nobushige Imai ◽  
Guersom Eduardo Ralda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Dependent Manner ◽  
Nad Kinase ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Thioredoxin 1 ◽  
Rate Limiting ◽  
Cultured Cardiomyocytes

Rationale: Diabetic cardiomyopathy is accompanied by increased production of NADH, predominantly through oxidation of fatty acids and consequent increases in oxidative stress. The role of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme of the salvage pathway of NAD + synthesis, in the development of diabetic cardiomyopathy is poorly understood. Objective: We investigated the role of endogenous and exogenous Nampt during the development of diabetic cardiomyopathy in response to high fat diet (HFD) consumption and in the context of oxidative stress. Methods and Results: HFD consumption upregulated endogenous Nampt, and HFD-induced cardiac diastolic dysfunction, fibrosis, apoptosis and pro-inflammatory signaling were alleviated in transgenic mice with cardiac-specific overexpression of Nampt. The alleviation of diastolic dysfunction observed in these mice was abolished by inhibition of NADP(H) production via NAD kinase (NADK) inhibition. Nampt overexpression decreased the GSSG/GSH ratio, oxidation of thioredoxin 1 (Trx1) targets, dityrosine, and the accumulation of toxic lipids, including ceramides and diglycerides, in the presence of HFD consumption. Nampt overexpression upregulated not only NAD + but also NADP + and NADPH in the heart and in cultured cardiomyocytes, which in turn stimulated the GSH and Trx1 systems and alleviated oxidative stress in the heart induced by HFD consumption. In cultured cardiomyocytes, Nampt-induced upregulation of NADPH was abolished in the presence of NADK knockdown, whereas that of NAD + was not. Nampt overexpression attenuated H 2 O 2 -induced oxidative inhibition of Prdx1 and mTOR in an NADK-dependent manner in cultured cardiomyocytes. Nampt overexpression also attenuated H 2 O 2 -induced cell death, an effect that was partly abolished by inhibition of NADK, Trx1 or GSH synthesis. In contrast, oxidative stress and the development of diabetic cardiomyopathy in response to HFD consumption were exacerbated in Nampt +/- mice. Conclusions: Nampt-mediated production of NAD + protects against oxidative stress in part through the NADPH-dependent reducing system, thereby alleviating the development of diabetic cardiomyopathy in response to HFD consumption.

scholarly journals Role of Oxidative Stress in Metabolic and Subcellular Abnormalities in Diabetic Cardiomyopathy

2020 ◽  
Vol 21 (7) ◽  
pp. 2413 ◽  
Author(s):  
Naranjan S. Dhalla ◽  
Anureet K. Shah ◽  
Paramjit S. Tappia
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Critical Role ◽  
Renin Angiotensin System ◽  
High Energy ◽  
Diabetic Heart ◽  
Therapeutic Approaches ◽  
Angiotensin System

Although the presence of cardiac dysfunction and cardiomyopathy in chronic diabetes has been recognized, the pathophysiology of diabetes-induced metabolic and subcellular changes as well as the therapeutic approaches for the prevention of diabetic cardiomyopathy are not fully understood. Cardiac dysfunction in chronic diabetes has been shown to be associated with Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+ and impaired sensitivity of myofibrils to Ca2+. Metabolic derangements, including depressed high-energy phosphate stores due to insulin deficiency or insulin resistance, as well as hormone imbalance and ultrastructural alterations, are also known to occur in the diabetic heart. It is pointed out that the activation of the sympathetic nervous system and renin–angiotensin system generates oxidative stress, which produces defects in subcellular organelles including sarcolemma, sarcoplasmic reticulum and myofibrils. Such subcellular remodeling plays a critical role in the pathogenesis of diabetic cardiomyopathy. In fact, blockade of the effects of neurohormonal systems has been observed to attenuate oxidative stress and occurrence of subcellular remodeling as well as metabolic abnormalities in the diabetic heart. This review is intended to describe some of the subcellular and metabolic changes that result in cardiac dysfunction in chronic diabetes. In addition, the therapeutic values of some pharmacological, metabolic and antioxidant interventions will be discussed. It is proposed that a combination therapy employing some metabolic agents or antioxidants with insulin may constitute an efficacious approach for the prevention of diabetic cardiomyopathy.

Role of 14-3-3 protein and oxidative stress in diabetic cardiomyopathy

2009 ◽  
Vol 96 (3) ◽  
pp. 277-287 ◽  
Author(s):  
Kenichi Watanabe ◽  
R. Thandavarayan ◽  
N. Gurusamy ◽  
S. Zhang ◽  
A. Muslin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
And Oxidative Stress

Oxidative stress: a key contributor to diabetic cardiomyopathyThis review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Madhu Khullar ◽  
Abd Al-Rahman S. Al-Shudiefat ◽  
Ana Ludke ◽  
Gursonika Binepal ◽  
Pawan K. Singal
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Contractile Function ◽  
Interstitial Fibrosis ◽  
Ion Homeostasis ◽  
Cardiovascular Morbidity And Mortality ◽  
Health And Disease ◽  
Heart Wall ◽  
Selection Of

Diabetes and its associated complications are major known health disorders. Diabetes mellitus increases the risk of cardiovascular morbidity and mortality by promoting cardiomyopathy. It appears to arise as a result of the diabetic state, at times independent of vascular or valvular pathology. It manifests initially as asymptomatic diastolic dysfunction, which progresses to symptomatic heart failure. The compliance of the heart wall is decreased and contractile function is impaired. The pathophysiology of diabetic cardiomyopathy is incompletely understood but appears to be multifactorial in origin. Several hypotheses have been proposed, including oxidative stress, inflammation, endothelial dysfunction, metabolic derangements, abnormalities in ion homeostasis, alterations in structural proteins, and interstitial fibrosis. Amongst these various mechanisms, an increase in reactive oxygen species, leading to oxidative stress, has received significant experimental support. This review focuses on the role of oxidative stress in the pathogenesis of diabetic cardiomyopathy and the potential of antioxidant therapy.

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