scholarly journals Cannabinoid 1 Receptor Promotes Cardiac Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in Diabetic Cardiomyopathy

Diabetes ◽  
2012 ◽  
Vol 61 (3) ◽  
pp. 716-727 ◽  
Author(s):  
M. Rajesh ◽  
S. Batkai ◽  
M. Kechrid ◽  
P. Mukhopadhyay ◽  
W.-S. Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Cannabinoid 1 Receptor

scholarly journals Cannabinoid 1 Receptor Promotes Cardiac Dysfunction, Oxidative Stress, Inflammation, and Fibrosis in Diabetic Cardiomyopathy

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
PAL PACHER ◽  
Mohanraj Rajesh ◽  
Sandor Batkai ◽  
Partha Mukhopadhyay ◽  
Wen‐Shin Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Cannabinoid 1 Receptor

scholarly journals GW27-e1129 RSVA314 attenuates cardiac dysfunction, oxidative stress, and inflammatory in diabetic cardiomyopathy

2016 ◽  
Vol 68 (16) ◽  
pp. C40-C41
Author(s):  
Gan Shouyi ◽  
Hui Yu ◽  
Hong-xia Huang ◽  
Bing Li ◽  
Ling-Yong Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction

scholarly journals CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats

Diabetologia ◽  
2017 ◽  
Vol 60 (6) ◽  
pp. 1126-1137 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Yu-Pei Yuan ◽  
Si-Chi Xu ◽  
Wen-Ying Wei ◽  
Chun-Ru Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction

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.

Nobiletin attenuates cardiac dysfunction, oxidative stress, and inflammatory in streptozotocin: induced diabetic cardiomyopathy

2016 ◽  
Vol 417 (1-2) ◽  
pp. 87-96 ◽  
Author(s):  
Ning Zhang ◽  
Zheng Yang ◽  
Shi-Zhao Xiang ◽  
Ya-Ge Jin ◽  
Wen-Ying Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction

Abstract 16563: FOXO1 Induces Cardiomyocyte-KLF5, Which Drives Oxidative Stress and Diabetic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ioannis D Kyriazis ◽  
Matthew K Hoffman ◽  
Lea Gaignebet ◽  
Anna Maria Lucchese ◽  
Chao Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Constitutive Expression ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Lipid Species ◽  
Ceramide Accumulation ◽  
Klf5 Expression

Introduction: Cardiomyopathy in type 1 diabetes (T1D) is accompanied by impaired mitochondrial function, oxidative stress and lipotoxicity. We showed that cardiomyocyte (CM) Krüppel-like factor 5 (KLF5) is increased in streptozotocin-induced T1D and induces Peroxisome Proliferator Activated Receptor (PPAR)α in mice. Hypothesis: KLF5 upregulation by FOXO1 induces diabetic cardiomyopathy (DbCM). Methods and Results: Analyses in CM from diabetic patients showed higher KLF5 mRNA levels compared to non-diabetic individuals. In vitro mechanistic and in vivo analyses in αMHC- Foxo1 -/- mice revealed that FOXO1 stimulates KLF5 expression via direct promoter binding. Genetic inhibition of CM FOXO1 alleviated DbCM. Additionally, AAV-mediated CM-specific KLF5 overexpression in C57Bl/6 (WT) mice induced cardiac dysfunction. Mice with CM-specific KLF5 constitutive expression (αMHC-rtTA- Klf5 ), which we generated, recapitulated cardiomyopathy without T1D. Moreover, Pparα -/- mice with T1D, had higher CM-KLF5 levels and developed DbCM, suggesting that KLF5-driven DbCM is PPARα-independent. Additionally, CM-KLF5 induced oxidative stress through increased NADPH oxidase (NOX)4 expression and lower mitochondria abundance. Conversely, KLF5 inhibition prevented NOX4 upregulation and superoxide formation. Furthermore, CM-KLF5 promoted NOX4 expression via direct promoter binding. Antioxidant treatment in diabetic WT and αMHC-rtTA- Klf5 mice alleviated cardiac dysfunction partially, suggesting other pathways that contribute in KLF5-induced DbCM. For that, we performed cardiac lipidome analysis where we found clustering of αMHC-rtTA- Klf5 with diabetic WT mice. Of note, KLF5 inhibition in diabetic mice resulted in similar lipidome with non-diabetic WT mice. Individual lipid species analysis showed increased ceramide accumulation in diabetic WT and αMHC-rtTA- Klf5 mice that was reversed upon KLF5 inhibition. Thus, CM-KLF5 activation correlates with cardiac ceramide accumulation, that has been associated with cardiac lipotoxicity. Conclusions: In conclusion, T1D stimulates FOXO1, which induces CM-KLF5 expression that leads to oxidative stress and DbCM in a non-PPARα-dependent manner, as well as to cardiac ceramide accumulation.

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.

scholarly journals Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy

2015 ◽  
Vol 87 ◽  
pp. 263-273 ◽  
Author(s):  
Prachi Umbarkar ◽  
Sarojini Singh ◽  
Silpa Arkat ◽  
S.L. Bodhankar ◽  
Sathiyanarayanan Lohidasan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Monoamine Oxidase ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Monoamine Oxidase A

scholarly journals GDF11 alleviates pathological myocardial remodeling in diabetic cardiomyopathy through SIRT1-dependent regulation of oxidative stress and apoptosis

2021 ◽  
Author(s):  
Hanzhao Zhu ◽  
Liyun Zhang ◽  
Mengen Zhai ◽  
Lin Xia ◽  
Yu Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Dysfunction ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Sirtuin 1 ◽  
H9c2 Cell ◽  
Diabetic Patients ◽  
Intramyocardial Injection

Abstract Background Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte injury, which induced by metabolic disorder. Nowadays, there is still a lack of drugs for the treatment of DCM. Growth differentiation factor 11 (GDF11) is a novel member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in DCM remain largely unknown. Methods In this study, we sought to determine whether GDF11 could prevent DCM. The mouse model of diabetes was established by administering a high-fat diet and intraperitoneal injecting streptozotocin. After that, intramyocardial injection of an adeno-associated virus carrying GDF11 gene was used to achieve myocardium-specific overexpression. Results Our data showed that GDF11 overexpression remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression was observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were also eliminated by SIRT1 depletion. Conclusion Our results demonstrated for the first time that GDF11 protected against DCM by regulating SIRT1 signaling pathway, and GDF11 had the potential to become a novel target for reversing cardiac dysfunction in diabetic patients.

Sign in / Sign up

Export Citation Format

Share Document