Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants

Prandi, Francesca Romana; Evangelista, Isabella; Sergi, Domenico; Palazzuoli, Alberto; Romeo, Francesco

doi:10.1007/s10741-021-10200-y

Cited by 36 publications

(31 citation statements)

References 57 publications

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“…The pathogenesis of cardiac fibrosis in DCM is complex, involving TGF-β, the renin-angiotensin-aldosterone system (RAAS), endothelin (ET), NO, vascular growth factor (VGF), Ca 2 + , and tissue inhibitors of metalloproteinases (TIMPs) ( 27 ). The endothelial-to-mesenchymal transition (EndMT) is also believed to be a significant mechanism of cardiac fibrosis in diabetes.…”

Section: Major Pathogenic Featuresmentioning

confidence: 99%

“…In the diabetic heart, OS also causes an increase in the intracellular Ca 2+ concentration and a reduction in sarcoplasmic Ca 2+ uptake, which are responsible for myocyte hypertrophy and also promote myocardial fibrosis ( 30 ). Finally, a high glucose concentration causes activation of the RAAS, leading to an increase in Ang II concentration, vascular resistance, and aldosterone secretion, which causes cardiomyocyte hypertrophy, hypertension, and the proliferation of cardiac fibroblasts ( 27 ).…”

Section: Major Pathogenic Featuresmentioning

confidence: 99%

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Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Peng

et al. 2022

Front. Endocrinol.

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Diabetes is a chronic metabolic disease that is increasing in prevalence and causes many complications. Diabetic cardiomyopathy (DCM) is a complication of diabetes that is associated with high mortality, but it is not well defined. Nevertheless, it is generally accepted that DCM refers to a clinical disease that occurs in patients with diabetes and involves ventricular dysfunction, in the absence of other cardiovascular diseases, such as coronary atherosclerotic heart disease, hypertension, or valvular heart disease. However, it is currently uncertain whether the pathogenesis of DCM is directly attributable to metabolic dysfunction or secondary to diabetic microangiopathy. Oxidative stress (OS) is considered to be a key component of its pathogenesis. The production of reactive oxygen species (ROS) in cardiomyocytes is a vicious circle, resulting in further production of ROS, mitochondrial DNA damage, lipid peroxidation, and the post-translational modification of proteins, as well as inflammation, cardiac hypertrophy and fibrosis, ultimately leading to cell death and cardiac dysfunction. ROS have been shown to affect various signaling pathways involved in the development of DCM. For instance, OS causes metabolic disorders by affecting the regulation of PPARα, AMPK/mTOR, and SIRT3/FOXO3a. Furthermore, OS participates in inflammation mediated by the NF-κB pathway, NLRP3 inflammasome, and the TLR4 pathway. OS also promotes TGF-β-, Rho-ROCK-, and Notch-mediated cardiac remodeling, and is involved in the regulation of calcium homeostasis, which impairs ATP production and causes ROS overproduction. In this review, we summarize the signaling pathways that link OS to DCM, with the intention of identifying appropriate targets and new antioxidant therapies for DCM.

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Section: Major Pathogenic Featuresmentioning

confidence: 99%

Section: Major Pathogenic Featuresmentioning

confidence: 99%

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Peng

et al. 2022

Front. Endocrinol.

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“…There is a significant relationship between the prevalence of heart failure and diabetes. In the absence of other traditional cardiac risk factors such as coronary artery disease, hypertension, and valvular heart disease, diabetes alone can cause heart failure, namely diabetic cardiomyopathy (DCM), presenting pathological changes in cardiac structure, metabolism, and function ( 187 ). In fact, diabetes is prevalent in anywhere between 10 and 40% of heart failure subjects due to cardiomyopathy ( 188 ).…”

Section: Cardiovascular and Other Complications In Diabetesmentioning

confidence: 99%

“…Although hyperglycemia, systemic insulin resistance, and hyperinsulinemia are regarded as the key etiological factors of DCM ( 187 ), multiple mechanisms may act at systemic, myocardial, and cellular/molecular levels, including metabolic abnormalities (e.g., lipotoxicity and glucotoxicity), mitochondrial damage and dysfunction, oxidative stress, abnormal calcium signaling, inflammation and epigenetic factors. For example, recent studies demonstrated in diabetic animal models that decreased cardiomyocyte function is a potential mechanism leading to DCM, which could result from decreased AMPK signaling, or increased AMP-activated protein kinase (MPK) signaling and increased protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling.…”

Section: Cardiovascular and Other Complications In Diabetesmentioning

confidence: 99%

“…A new study using multi-omics technology in a HFD-STZ model showed that the formation of short-chain acylcarnitine species in T2D mouse hearts activated networks to redistribute excess acetyl-CoA toward ketogenesis and incomplete β-oxidation, resulting in loss of metabolic flexibility and the capacity of the heart to respond to subsequent cardiovascular events ( 197 ). Clearly, these disturbances would predispose the heart to extracellular remodeling and hypertrophy, both eventually leading to heart failure ( 187 ). Along with the deleterious hyperglycemic and hyperlipidemic effects on DCM, immerging research has analyzed the impact of HFD-induced diabetes on cardiac dysfunction in the context of lipotoxicity ( 198 ).…”

Section: Cardiovascular and Other Complications In Diabetesmentioning

confidence: 99%

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Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses

Norton

Cui

et al. 2022

Front. Cardiovasc. Med.

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Diabetes mellitus is a worldwide health problem that usually comes with severe complications. There is no cure for diabetes yet and the threat of these complications is what keeps researchers investigating mechanisms and treatments for diabetes mellitus. Due to advancements in genomics, epigenomics, proteomics, and single-cell multiomics research, considerable progress has been made toward understanding the mechanisms of diabetes mellitus. In addition, investigation of the association between diabetes and other physiological systems revealed potentially novel pathways and targets involved in the initiation and progress of diabetes. This review focuses on current advancements in studying the mechanisms of diabetes by using genomic, epigenomic, proteomic, and single-cell multiomic analysis methods. It will also focus on recent findings pertaining to the relationship between diabetes and other biological processes, and new findings on the contribution of diabetes to several pathological conditions.

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NF‐κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation

Zamanian,

Alsaab,

Golmohammadi

et al. 2024

Cell Biochemistry & Function

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Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF‐κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF‐α) and interleukin‐6 (IL‐6), by modulating the NF‐κB signaling pathway. By reducing the expression of these inflammatory factors, CUR demonstrates protective effects in DM by improving pancreatic β‐cells function, normalizing inflammatory cytokines, reducing OS and enhancing insulin sensitivity. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin ‐induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as calcium–calmodulin (CaM)‐dependent protein kinase II (CaMKII), peroxisome proliferator‐activated receptor gamma (PPAR‐γ), NF‐κB, and transforming growth factor β1 (TGFB1). Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF‐α, Interleukin‐1 beta (IL‐1β), IL‐6) and chemokines like MCP‐1 in diabetic specimens, vindicating its anti‐inflammatory potency in counteracting hyperglycemia‐induced alterations. CUR diminishes OS, avert structural kidney damage linked to diabetic nephropathy, and suppress NF‐κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF‐κB pathway.

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Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants

Cited by 36 publications

References 57 publications

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses

NF‐κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation

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