Molecular Mechanisms in the Pathogenesis of Diabetic Cardiomyopathy

2011 ◽  
pp. 365-378
Author(s):  
Subrata Chakrabarti
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms

scholarly journals Identification of Core Gene Biomarkers in Patients with Diabetic Cardiomyopathy

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ning Li ◽  
Haiming Wu ◽  
Rongxin Geng ◽  
Qizhu Tang
Keyword(s):  
Western Blot ◽  
Diabetic Cardiomyopathy ◽  
Protein Level ◽  
Molecular Mechanisms ◽  
Cardiac Fibroblasts ◽  
Core Gene ◽  
Cardiomyocyte Hypertrophy ◽  
Diabetic Patients ◽  
Ppi Network

Diabetic cardiomyopathy (DCM) is a disorder of the myocardium in diabetic patients, which is one of the critical complications of diabetes giving rise to an increased mortality. However, the underlying mechanisms of DCM remain incompletely understood presently. This study was designed to screen the potential molecules and pathways implicated with DCM. GSE26887 involving 5 control individuals and 7 DCM patients was selected from the GEO database to identify the differentially expressed genes (DEGs). DAVID was applied to perform gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was also constructed to visualize the interactions among these DEGs. To further validate significant genes and pathways, quantitative real-time PCR (qPCR) and Western blot were performed. A total of 236 DEGs were captured, including 134 upregulated and 102 downregulated genes. GO, KEGG, and the PPI network disclosed that inflammation, immune disorders, metabolic disturbance, and mitochondrial dysfunction were significantly enriched in the development of DCM. Notably, IL6 was an upregulated hub gene with the highest connectivity degree, suggesting that it may interact with a great many molecules and pathways. Meanwhile, SOCS3 was also one of the top 15 hub genes in the PPI network. Herein, we detected the protein level of STAT3 and SOCS3 in a mouse model with DCM. Western blot results showed that the protein level of SOCS3 was significantly lower while phosphorylated-STAT3 (P-STAT3) was activated in mice with DCM. In vitro results also uncovered the similar alterations of SOCS3 and P-STAT3 in cardiomyocytes and cardiac fibroblasts induced by high glucose (HG). However, overexpression of SOCS3 could significantly reverse HG-induced cardiomyocyte hypertrophy and collagen synthesis of cardiac fibroblasts. Taken together, our analysis unveiled potential biomarkers and molecular mechanisms in DCM, which could be helpful to the diagnosis and treatment of DCM.

scholarly journals Molecular mechanisms of diastolic dysfunction in diabetic cardiomyopathy

2019 ◽  
Vol 92 (0) ◽  
pp. 3-O-04
Author(s):  
Yoshinori Mikami ◽  
Shogo Hamaguchi ◽  
Masanori Ito ◽  
Shingo Murakami ◽  
Taichiro Tomida ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms

scholarly journals Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Felipe Muñoz-Córdova ◽  
Carolina Hernández-Fuentes ◽  
Camila Lopez-Crisosto ◽  
Mayarling F. Troncoso ◽  
Ximena Calle ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Clinical Manifestations ◽  
Myocardial Cell ◽  
Cardiomyocyte Hypertrophy ◽  
Autophagic Flux ◽  
Low Grade ◽  
Cellular Processes ◽  
Pharmacological Targets

Diabetic cardiomyopathy (DCM) is a severe complication of diabetes developed mainly in poorly controlled patients. In DCM, several clinical manifestations as well as cellular and molecular mechanisms contribute to its phenotype. The production of reactive oxygen species (ROS), chronic low-grade inflammation, mitochondrial dysfunction, autophagic flux inhibition, altered metabolism, dysfunctional insulin signaling, cardiomyocyte hypertrophy, cardiac fibrosis, and increased myocardial cell death are described as the cardinal features involved in the genesis and development of DCM. However, many of these features can be associated with broader cellular processes such as inflammatory signaling, mitochondrial alterations, and autophagic flux inhibition. In this review, these mechanisms are critically discussed, highlighting the latest evidence and their contribution to the pathogenesis of DCM and their potential as pharmacological targets.

scholarly journals Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Anupam Mittal ◽  
Rajni Garg ◽  
Ajay Bahl ◽  
Madhu Khullar
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Cardiac Metabolism ◽  
Molecular Pathways ◽  
Myocardial Apoptosis ◽  
Epigenetic Modifiers ◽  
Artery Disease ◽  
And Function ◽  
Lifestyle Disease

Diabetes mellitus (DM) is an important lifestyle disease. Type 2 diabetes is one of the prime contributors to cardiovascular diseases (CVD) and diabetic cardiomyopathy (DbCM) and leads to increased morbidity and mortality in patients with DM. DbCM is a typical cardiac disease, characterized by cardiac remodeling in the presence of DM and in the absence of other comorbidities such as hypertension, valvular diseases, and coronary artery disease. DbCM is associated with defective cardiac metabolism, altered mitochondrial structure and function, and other physiological and pathophysiological signaling mechanisms such as oxidative stress, inflammation, myocardial apoptosis, and autophagy. Epigenetic modifiers are crucial players in the pathogenesis of DbCM. Thus, it is important to explore the role of epigenetic modifiers or modifications in regulating molecular pathways associated with DbCM. In this review, we have discussed the role of various epigenetic mechanisms such as histone modifications (acetylation and methylation), DNA methylation and non-coding RNAs in modulating molecular pathways involved in the pathophysiology of the DbCM.

scholarly journals Mitophagy in Diabetic Cardiomyopathy: Roles and Mechanisms

2021 ◽  
Vol 9 ◽  
Author(s):  
Haoxiao Zheng ◽  
Hailan Zhu ◽  
Xinyue Liu ◽  
Xiaohui Huang ◽  
Anqing Huang ◽  
...  
Keyword(s):  
Quality Control ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Myocardial Damage ◽  
Diabetic Heart ◽  
Substantial Contribution ◽  
Diabetic Patients ◽  
Mitochondrial Quality Control ◽  
Comprehensive Overview ◽  
Myocardial Insulin Resistance

Cardiovascular disease is the leading complication of diabetes mellitus (DM), and diabetic cardiomyopathy (DCM) is a major cause of mortality in diabetic patients. Multiple pathophysiologic mechanisms, including myocardial insulin resistance, oxidative stress and inflammation, are involved in the development of DCM. Recent studies have shown that mitochondrial dysfunction makes a substantial contribution to the development of DCM. Mitophagy is a type of autophagy that takes place in dysfunctional mitochondria, and it plays a key role in mitochondrial quality control. Although the precise molecular mechanisms of mitophagy in DCM have yet to be fully clarified, recent findings imply that mitophagy improves cardiac function in the diabetic heart. However, excessive mitophagy may exacerbate myocardial damage in patients with DCM. In this review, we aim to provide a comprehensive overview of mitochondrial quality control and the dual roles of mitophagy in DCM. We also propose that a balance between mitochondrial biogenesis and mitophagy is essential for the maintenance of cellular metabolism in the diabetic heart.

Curcumin attenuates palmitic acid-induced cell apoptosis by inhibiting endoplasmic reticulum stress in H9C2 cardiomyocytes

2019 ◽  
Vol 38 (6) ◽  
pp. 655-664 ◽  
Author(s):  
G Guan ◽  
L Lei ◽  
Q Lv ◽  
Y Gong ◽  
L Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Expression ◽  
Cell Viability ◽  
Palmitic Acid ◽  
Er Stress ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Protective Action ◽  
H9c2 Cardiomyocytes

Diabetic cardiomyopathy is mediated by multiple molecular mechanisms including endoplasmic reticulum (ER) stress. Curcumin, a phenolic compound, has cytoprotective properties, but its potential protective action against diabetic cardiomyopathy and the related molecular mechanisms are not fully elucidated. In this study, we evaluated the effects of curcumin on cell viability and apoptosis in palmitic acid (PA)-treated H9C2 cardiomyocytes and investigated the signaling pathways involved. Treatment with PA reduced cell viability, induced apoptosis, enhanced apoptosis-related protein expression (Caspase 3 and BCL-2 associated X protein (BAX)), and activated ER stress marker protein expression (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Curcumin attenuated PA-induced reduction in cell viability and activation of apoptosis, Caspase 3 activity, BAX, CHOP, and GRP78 expression. 4-Phenylbutyric acid (4-PBA) attenuated the PA-induced effects on cell viability and apoptosis, similar to curcumin. Both curcumin and 4-PBA also attenuated PA-induced increase in ER stress protein (CHOP and GRP78) expression. Curcumin also protected against cytotoxicity, apoptosis, and ER stress induced by thapsigargin. These findings indicate that PA triggers apoptosis in H9C2 cells via ER stress pathways and curcumin protects against this phenomenon.

scholarly journals Research('s) Sweet Hearts: Experimental Biomedical Models of Diabetic Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Claudia Richter ◽  
Rabea Hinkel
Keyword(s):  
Animal Models ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Cellular Responses ◽  
Genetic Alterations ◽  
Rodent Models ◽  
Therapeutic Approaches ◽  
Advantages And Disadvantages ◽  
Shed Light

Diabetes and the often accompanying cardiovascular diseases including cardiomyopathy represent a complex disease, that is reluctant to reveal the molecular mechanisms and underlying cellular responses. Current research projects on diabetic cardiomyopathy are predominantly based on animal models, in which there are not only obvious advantages, such as genetics that can be traced over generations and the directly measurable influence of dietary types, but also not despisable disadvantages. Thus, many studies are built up on transgenic rodent models, which are partly comparable to symptoms in humans due to their genetic alterations, but on the other hand are also under discussion regarding their clinical relevance in the translation of biomedical therapeutic approaches. Furthermore, a focus on transgenic rodent models ignores spontaneously occurring diabetes in larger mammals (such as dogs or pigs), which represent with their anatomical similarity to humans regarding their cardiovascular situation appealing models for testing translational approaches. With this in mind, we aim to shed light on the currently most popular animal models for diabetic cardiomyopathy and, by weighing the advantages and disadvantages, provide decision support for future animal experimental work in the field, hence advancing the biomedical translation of promising approaches into clinical application.

scholarly journals Forskolin Protected against Streptozotocin-Induced Diabetic Cardiomyopathy via Inhibition of Oxidative Stress and Cardiac Fibrosis in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xu Zhang ◽  
Pei-Xiong Ke ◽  
Xun Yuan ◽  
Gui-Ping Zhang ◽  
Wen-Liang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Morphological Changes ◽  
Cardiac Complications ◽  
Pathological Feature ◽  
Diabetes In Mice ◽  
Cardiac Functions ◽  
Commercial Kits

Background. Diabetic cardiomyopathy is one of the cardiac complications in diabetes patients, eventually resulting in heart failure and increasing morbidity and mortality. Oxidative stress is a critical pathological feature in diabetic hearts, contributing to the development of DCM. Forskolin (FSK) was shown to reduce oxidative stress. This study was aimed at investigating the effects of FSK on diabetic hearts and the relevant molecular mechanisms. Methods. Streptozotocin- (STZ-) induced diabetes in mice was treated with FSK through intraperitoneal injection. Cardiac functions were evaluated by echocardiography. Hematoxylin-eosin and Masson trichrome staining was employed to determine heart morphological changes and cardiac fibrosis, respectively. Cardiac fibrosis-related markers were detected by western blot. Superoxide dismutase activity, reduced/oxidized glutathione ratio, and malondialdehyde concentration in left ventricles were determined using respective commercial kits. Results. Abnormal cardiac diastolic dysfunction and cardiac fibrosis were observed in diabetic hearts. FSK treatment significantly improved the cardiac diastolic function and attenuated the abnormal morphological change in diabetic hearts. Moreover, FSK treatment in diabetic mice decreased the expression of fibronectin, collagen I, TGF-β, and α-SMA and reduced myocardial fibrosis. Furthermore, we observed that FSK significantly blocked oxidative stress in diabetic hearts. Conclusions. Our study demonstrates that FSK protects against the development of DCM in STZ-induced diabetes in mice. Our study suggests that FSK might be a potential target for drug development in treating DCM.

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