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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Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: April 13, 2023

Abstract Among the complications of diabetes, cardiovascular events and cardiac insufficiency are considered two most important causes death. Experimental clinical evidence supports effectiveness SGLT2i for improving dysfunction. treatment benefits metabolism, microcirculation, mitochondrial function, fibrosis, oxidative stress, endoplasmic reticulum programmed cell death, autophagy, intestinal flora, which involved in diabetic cardiomyopathy. This review summarizes current knowledge mechanisms Graphical

Language: Английский

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Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Oct. 11, 2022

Abstract Background Diabetic cardiomyopathy is characterized by left ventricle dysfunction, cardiomyocyte apoptosis, and interstitial fibrosis a serious complication of diabetes mellitus (DM). Autophagy mechanism that essential for maintaining normal heart morphology function, its dysregulation can produce pathological effects on diabetic hearts. Neuregulin-4 (Nrg4) an adipokine exerts protective against metabolic disorders insulin resistance. The aim this study was to explore whether Nrg4 could ameliorate DM-induced myocardial injury regulating autophagy. Methods Four weeks after the establishment model type 1 in mice, mice received treatment (with or without autophagy inhibitor) another 4 weeks. cardiac functions, histological structures apoptosis were investigated. Autophagy-related protein levels along with related signalling pathways regulate evaluated. In addition, also determined cultured primary cardiomyocytes. Results alleviated both vivo vitro. level decreased intervention reactivated Furthermore, found activate via AMPK/mTOR pathway. Moreover, when suppressed pathway inhibited, beneficial diminished. Conclusion attenuated promoting mice. Additionally, induced

Language: Английский

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The Pathophysiological Basis of Diabetic Cardiomyopathy Development

Current Problems in Cardiology, Journal Year: 2022, Volume and Issue: 47(9), P. 101156 - 101156

Published: Feb. 19, 2022

Language: Английский

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USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart

Circulation, Journal Year: 2023, Volume and Issue: 149(9), P. 684 - 706

Published: Nov. 23, 2023

BACKGROUND: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role therapeutic value USP28 (ubiquitin-specific protease 28) on metabolic vulnerability cardiomyopathy. METHODS: type 2 mouse model was established using db/db leptin receptor–deficient mice high-fat diet/streptozotocin–induced mice. Cardiac-specific knockout in background generated by crossbreeding db/m Myh6-Cre + /USP28 fl/fl Recombinant adeno-associated virus serotype 9 carrying under troponin T promoter injected into High glucose plus palmitic acid–incubated neonatal rat ventricular myocytes human induced pluripotent stem cell-derived cardiomyocytes were used imitate vitro. molecular mechanism explored through RNA sequencing, immunoprecipitation mass spectrometry analysis, protein pull-down, chromatin assay. RESULTS: Microarray profiling UPS (ubiquitin-proteasome system) basis hearts patients’ demonstrated that ventricle presented a significant reduction expression. Diabetic exhibited more severe progressive dysfunction, lipid accumulation, mitochondrial disarrangement, compared their controls. On other hand, overexpression improved systolic diastolic ameliorated hypertrophy fibrosis heart. Adeno-associated 9-USP28 also less storage, reduced reactive oxygen species formation, impairment tissues than 9-null As result, attenuated remodeling These results confirmed cell–derived cardiomyocytes. assays, pull-down assay mechanistically revealed directly interacted PPARα (peroxisome proliferator–activated receptor α), deubiquitinating stabilizing (Lys152) promote Mfn2 (mitofusin 2) transcription, thereby impeding morphofunctional defects. However, such cardioprotective benefits largely abrogated deletion conditional loss-of-function Mfn2. CONCLUSIONS: Our findings provide USP28-modulated mitochondria homeostasis involves PPARα-Mfn2 axis hearts, suggesting activation or targeting represents strategy for

Language: Английский

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Exploring the Complex Relationship between Diabetes and Cardiovascular Complications: Understanding Diabetic Cardiomyopathy and Promising Therapies

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1126 - 1126

Published: April 7, 2023

Diabetes mellitus (DM) and cardiovascular complications are two unmet medical emergencies that can occur together. The rising incidence of heart failure in diabetic populations, addition to apparent coronary disease, ischemia, hypertension-related complications, has created a more challenging situation. Diabetes, as predominant cardio-renal metabolic syndrome, is related severe vascular risk factors, it underlies various complex pathophysiological pathways at the molecular level progress converge toward development cardiomyopathy (DCM). DCM involves several downstream cascades cause structural functional alterations heart, such diastolic dysfunction progressing into systolic dysfunction, cardiomyocyte hypertrophy, myocardial fibrosis, subsequent over time. effects glucagon-like peptide-1 (GLP-1) analogues sodium-glucose cotransporter-2 (SGLT-2) inhibitors on (CV) outcomes diabetes have shown promising results, including improved contractile bioenergetics significant benefits. purpose this article highlight pathophysiological, metabolic, contribute its cardiac morphology functioning. Additionally, will discuss potential therapies may be available future.

Language: Английский

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Mitochondrial quality control in health and cardiovascular diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Nov. 6, 2023

Cardiovascular diseases (CVDs) are one of the primary causes mortality worldwide. An optimal mitochondrial function is central to supplying tissues with high energy demand, such as cardiovascular system. In addition producing ATP a power source, mitochondria also heavily involved in adaptation environmental stress and fine-tuning tissue functions. Mitochondrial quality control (MQC) through fission, fusion, mitophagy, biogenesis ensures clearance dysfunctional preserves homeostasis tissues. Furthermore, generate reactive oxygen species (ROS), which trigger production pro-inflammatory cytokines regulate cell survival. dysfunction has been implicated multiple CVDs, including ischemia-reperfusion (I/R), atherosclerosis, heart failure, cardiac hypertrophy, hypertension, diabetic genetic cardiomyopathies, Kawasaki Disease (KD). Thus, MQC pivotal promoting health. Here, we outline mechanisms discuss current literature on CVDs.

Language: Английский

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N-acetylcysteine Protects Against Myocardial Ischemia–Reperfusion Injury Through Anti-ferroptosis in Type 1 Diabetic Mice

Cardiovascular Toxicology, Journal Year: 2024, Volume and Issue: 24(5), P. 481 - 498

Published: April 22, 2024

Abstract The hearts of subjects with diabetes are vulnerable to ischemia–reperfusion injury (IRI). In contrast, experimentally rodent have been shown be more resistant IRI at the very early stages induction than heart non-diabetic control mice, and mechanism is largely unclear. Ferroptosis has recently play an important role in myocardial including that diabetes, while specific mechanisms still Non-diabetic (NC) streptozotocin-induced diabetic (DM) mice were treated antioxidant N-acetylcysteine (NAC) drinking water for 4 week starting 1 after induction. Mice subjected induced by occluding coronary artery 30 min followed 2 h reperfusion, subsequently 1, 2, 5 post-ischemic infarct size DM was smaller NC but greater which associated a significant increase ferroptosis reduction diabetes. NAC significantly attenuated as well oxidative stress reduced Application erastin, inducer, reversed cardioprotective effects NAC. It concluded increased major factors attributable vulnerability attenuation represents whereby confers cardioprotection against

Language: Английский

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Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway

Journal of Diabetes Research, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 11

Published: Dec. 31, 2022

The present study investigated whether quercetin promotes the nuclear translocation of factor erythroid-2-related 2 (Nrf2) to inhibit pyroptosis progression and ameliorate diabetic cardiomyopathy. We evaluated protective effects against cardiomyopathy by analyzing expression pathway proteins, myocardial cell apoptosis rate, degree fibrosis, serum inflammatory indices in hearts model rats with diabetes. Nrf2 nucleus cardiomyocytes H9C2 cells clarify role promoting Nrf2. In addition, we coincubated inhibitor ML385 confirm that inhibits diabetes-induced cardiomyocyte via pathway. found promoted cardiac rats, increased antioxidant proteins HO-1, GCLC, SOD, reduced accumulation ROS apoptosis, alleviated fibrosis. therapeutic were further validated cardiomyocytes. Interestingly, prevented beneficial on cardiomyopathy, indicating quercetin-mediated inhibition requires participation conclusion, Nrf2, factors cells, inhibited pyroptosis, thereby alleviating

Language: Английский

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PRDM16 exerts critical role in myocardial metabolism and energetics in type 2 diabetes induced cardiomyopathy

Metabolism, Journal Year: 2023, Volume and Issue: 146, P. 155658 - 155658

Published: July 9, 2023

Language: Английский

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