Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: June 15, 2022

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

Language: Английский

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Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING signaling dependent on LKB1/AMPK/ULK1-mediated autophagy

Journal of Advanced Research, Journal Year: 2022, Volume and Issue: 51, P. 161 - 179

Published: Nov. 10, 2022

Meteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles obesity, insulin resistance, inflammation. Metrnl found to protect against cardiac hypertrophy doxorubicin-induced cardiotoxicity. However, its role diabetic cardiomyopathy (DCM) undefined.We aimed elucidate the potential of DCM.Gain- andloss-of-function experimentswere utilized determine pathological processes DCM.We that plasma levels, myocardial protein mRNA expressions were significantly downregulated both streptozotocin (STZ)-induced (T1D) mice leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression (OE) markedly ameliorated injury dysfunction T1D T2D In sharp contrast, specific deletion heart had opposite phenotypes. parallel, OE ameliorated, whereas downregulation exacerbated high glucose (HG)-elicited hypertrophy, apoptosis oxidative damage primary neonatal rat cardiomyocytes. Antibody-induced blockade eliminated effects benefits vitro vivo. Mechanistically, activated autophagy pathway inhibited cGAS/STING signaling a LKB1/AMPK/ULK1-dependent mechanism Besides, Metrnl-induced ULK1 phosphorylation facilitated dephosphorylation mitochondrial translocation STING where it interacted tumor necrosis factor receptor-associated 2 (TRAF2), scaffold E3 ubiquitin ligase was responsible for ubiquitination degradation STING, rendering cardiomyocytes sensitive activation.Thus, may be an attractive therapeutic target or regimen treating DCM.

Language: Английский

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Innate metabolic responses against viral infections

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(10), P. 1245 - 1259

Published: Oct. 20, 2022

Language: Английский

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Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: July 21, 2023

Abstract Diabetic cardiomyopathy (DCM) mainly refers to myocardial metabolic dysfunction caused by high glucose, and hyperglycemia is an independent risk factor for cardiac function in the absence of coronary atherosclerosis hypertension. DCM, which a severe complication diabetes, has become leading cause heart failure diabetic patients. The initial symptoms are inconspicuous, patients gradually exhibit left ventricular eventually develop total failure, brings great challenge early diagnosis DCM. To date, underlying pathological mechanisms DCM complicated have not been fully elucidated. Although there therapeutic strategies available treatment focused on controlling blood glucose lipids, lack effective drugs targeting injury. Thus, large percentage with inevitably failure. Given neglected symptoms, intricate cellular molecular mechanisms, drugs, it necessary explore diagnostic biomarkers, further understand signaling pathways involved pathogenesis summarize current strategies, new targeted interventions.

Language: Английский

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Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 1, 2023

Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications diabetes and a leading cause death in diabetic patients. Mitochondrial metabolism immune-inflammation are key for DCM pathogenesis, but their crosstalk remains an open issue. This study explored separate roles mitochondrial immune microenvironment with bioinformatics.DCM chip data (GSE4745, GSE5606, GSE6880) were obtained from NCBI GEO, while gene downloaded MitoCarta3.0 database. Differentially expressed genes (DEGs) screened by GEO2R processed GSEA, GO KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) obtained. A PPI network was constructed, hub MitoDEGs closely linked to or heart failure identified CytoHubba, MCODE CTD scores. Transcription factors target miRNAs predicted Cytoscape miRWalk database, respectively, regulatory established. The infiltration pattern analyzed ImmuCellAI, relationship between abundance investigated using Spearman method. rat model established validate expression cardiac function.MitoDEGs significantly enriched pathways involved metabolism, immunoregulation, collagen synthesis. Nine Immune analysis revealed increased B cells decreased DCs DCM. demonstrated that positively associated pro-inflammatory cells, negatively anti-inflammatory cells. In animal experiment, 4 (Pdk4, Hmgcs2, Decr1, Ivd) showed trend consistent bioinformatics result. Additionally, up-regulation Pdk4, Decr1 down-regulation Ivd distinctly reduced function.This unraveled interaction DCM, providing new insights into research on potential pathogenesis exploration novel targets medical interventions.

Language: Английский

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Cadmium exposure caused cardiotoxicity in common carps (Cyprinus carpio L.): miR-9-5p, oxidative stress, energetic impairment, mitochondrial division/fusion imbalance, inflammation, and autophagy

Fish & Shellfish Immunology, Journal Year: 2023, Volume and Issue: 138, P. 108853 - 108853

Published: May 27, 2023

Language: Английский

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Functionalized Metal–Organic Framework‐Modified Hydrogel That Breaks the Vicious Cycle of Inflammation and ROS for Repairing of Diabetic Bone Defects

Small, Journal Year: 2023, Volume and Issue: 19(36)

Published: May 14, 2023

The regeneration of diabetic bone defects remains challenging. Hyperglycemia causes inflammation state and excessive reactive oxygen species (ROS) during period. These two effects reinforce one another create an endless loop that is also accompanied by mitochondrial dysfunction. However, there still no effective inclusive method targeting at the aspects breaking vicious cycle. Herein, nanoparticles-Met@ZIF-8(metformin loaded zeolitic imidazolate frameworks) modified hydrogel capable releasing metformin Zn elements are constructed. This treats hyperglycemia while controlling function, reducing inflammation, restoring homeostasis. In addition, synergetic effect from ions inhibits ROS-inflammation cascade generation destroys continuous progress taking in both ROS further keeping organelles' Furthermore, with recovery mitochondria breakdown cycle, osteogenesis under a microenvironment enhanced vivo vitro. conclusion, study provides critical insight into biological mechanism potential therapy for regeneration.

Language: Английский

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Pyroptosis in health and disease: mechanisms, regulation and clinical perspective

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

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Metformin-based nanomedicines for reprogramming tumor immune microenvironment

Theranostics, Journal Year: 2024, Volume and Issue: 15(3), P. 993 - 1016

Published: Dec. 2, 2024

Immunotherapy has transformed current cancer management, and it achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing activity immune cells facilitating immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator cellular energy metabolism homeostasis, gained growing attention in anti-tumor immunity. Metformin is usually considered as cornerstone diabetes its role activating AMPK pathway also been extensively explored therapy although findings on remain inconsistent. nanomedicine formulation found to hold potential reprogramming TME through immunometabolic modulation both cells. This review elaborates foundation via metformin-based nanomedicines, offering valuable insights for next generation therapy.

Language: Английский

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Mitophagy in Cardiovascular Diseases

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(3), P. 892 - 892

Published: March 24, 2020

Cardiovascular diseases are one of the leading causes death. Increasing evidence has shown that pharmacological or genetic targeting mitochondria can ameliorate each stage these pathologies, which strongly associated with mitochondrial dysfunction. Removal inefficient and dysfunctional through process mitophagy been reported to be essential for meeting energetic requirements maintaining biochemical homeostasis cells. This is useful counteracting negative phenotypic changes occur during cardiovascular diseases, understanding molecular players involved might crucial development potential therapies. Here, we summarize current knowledge on (and autophagy) mechanisms in context heart disease an important focus atherosclerosis, ischemic disease, cardiomyopathies, failure, hypertension, arrhythmia, congenital peripheral vascular disease. We aim provide a complete background action this quality control cardiology cardiac surgery by also reviewing studies use known compounds able modulate cardioprotective purposes.

Language: Английский

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