The mechanisms of ferroptosis and its role in atherosclerosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116112 - 116112

Published: Jan. 2, 2024

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.

Language: Английский

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Ferroptosis: mechanisms and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(12)

Published: Nov. 20, 2024

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification 2012, extensive research has unveiled involvement the pathophysiology numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious autoimmune conditions, metabolic and skin diseases. Oxidizable lipids, overload iron, compromised antioxidant systems are known as critical prerequisites for driving overwhelming peroxidation, ultimately leading to plasma rupture ferroptotic death. However, precise regulatory networks governing ferroptosis ferroptosis-targeted therapy these diseases remain largely undefined, hindering development pharmacological agonists antagonists. In this review, we first elucidate core mechanisms summarize epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, N6-methyladenosine modification) nonepigenetic genetic mutations, transcriptional regulation, posttranslational modifications). We then discuss association between disease pathogenesis explore therapeutic approaches targeting ferroptosis. also introduce potential clinical monitoring strategies Finally, put forward several unresolved issues which progress needed better understand hope review will offer promise application therapies context human health disease.

Language: Английский

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Ferroptosis induced by environmental pollutants and its health implications

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 24, 2025

Abstract Environmental pollution represents a significant public health concern, with the potential risks associated environmental pollutants receiving considerable attention over an extended period. In recent years, substantial body of research has been dedicated to this topic. Since discovery ferroptosis, iron-dependent programmed cell death typically characterized by lipid peroxidation, in 2012, there have advances study its role and mechanism various diseases. A growing number studies also demonstrated involvement ferroptosis damage caused organism pollutants, molecular mechanisms involved partially elucidated. The targeting be effective means ameliorating PM2.5, organic inorganic ionizing radiation. This review begins providing summary most important ferroptosis. It then proceeds offer critical analysis effects induced pollutants. Furthermore, as is case all rapidly evolving areas, are numerous unanswered questions challenges pertaining pollutant-induced which we discuss attempt provide some directions clues for future field.

Language: Английский

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Application of natural products in regulating ferroptosis in human diseases

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155384 - 155384

Published: Jan. 28, 2024

Language: Английский

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Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(3), P. 1623 - 1650

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer‐related mortality, continues to pose significant challenges in realm medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy‐related signaling as a promising avenue for HCC treatment. A growing body research has highlighted pivotal role autophagy‐modulating natural products inhibiting progression. In this context, we provide concise overview fundamental autophagy mechanism delineate involvement autophagic pathways development. Additionally, review pertinent studies demonstrating how regulate mitigate HCC. Our findings indicate that exhibit cytotoxic effects through induction excessive autophagy, simultaneously impeding cell proliferation by inhibition, thereby depriving cells essential energy. These been associated with various pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β‐catenin, Beclin‐1, ferroautophagy. results underscore considerable therapeutic potential However, it is important note present study did not establish definitive thresholds or inhibition products. Further domain imperative gain comprehensive insights into dual equipping us better understanding double‐edged sword management.

Language: Английский

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Fibroblast growth factor 21 improves diabetic cardiomyopathy by inhibiting ferroptosis via ferritin pathway

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 2, 2024

Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 2 diabetes mellitus, and its mechanisms are complex poorly understood. Despite growing evidence suggesting that ferroptosis plays significant role cardiovascular disease, it has been less extensively studied DCM. Fibroblast growth factor 21 (FGF21), whose mechanism of action closely related to ferroptosis, widely utilized studies focused on the prevention treatment glucolipid metabolism-related diseases diseases. To confirm DCM investigate whether FGF21 improves by inhibiting elucidating specific molecular mechanisms. The animal models were established through high-fat feeding combined streptozotocin injection C57BL/6J mice or db/db mice, diabetic cardiomyocyte injury model was created using high glucose fat (HG/HF) culture primary cardiomyocytes. Intervention modeling performed injecting adeno-associated virus 9-FGF21 transfecting siRNA overexpression plasmid findings indicated exacerbated played inhibited improved cardiac function, whereas knockdown aggravated function Furthermore, we discovered directly acting ferritin prolonging half-life. Specifically, binded heavy light chains ferritin, thereby reducing excessive degradation proteasome lysosomal-autophagy pathways Additionally, activating transcription 4 (ATF4) served as upstream regulator ATF4-FGF21-ferritin axis mediates protective effects pathway represents potential therapeutic target for

Language: Английский

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Immunotherapy Study on Non-small-Cell Lung Cancer (NSCLC) Combined with Cytotoxic T Cells and miRNA34a

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(3), P. 1364 - 1381

Published: Jan. 31, 2024

Immunotherapy has emerged as a promising approach for cancer treatment, and the use of microRNAs (miRNAs) therapeutic agents gained significant attention. In this study, we investigated effectiveness immunotherapy utilizing miRNA34a Jurkat T cells in inducing cell death non-small-cell lung cells, specifically A549 cells. Moreover, explored impact activation delivery using iron oxide nanorods (IONRs) on killing were cocultured with both activated inactivated before after miRNA34a. Surprisingly, our results revealed that even inactive capable This unexpected observation suggested presence alternative mechanisms by which can exert cytotoxic effects We stimulated anti-CD3/CD28 analyzed their efficacy compared to conjunction Our findings indicated significantly enhanced potential against counterparts. The combined treatment demonstrated highest level death, suggesting synergistic effect between miRNA therapy. Besides apoptosis mechanism cells' furthermore ferroptosis pathway, was found have an due IONRs agent inside

Language: Английский

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High Hepcidin Levels Promote Abnormal Iron Metabolism and Ferroptosis in Chronic Atrophic Gastritis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2338 - 2338

Published: Aug. 22, 2023

Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance susceptible to inflammation. Objectives: The objective this study was clarify whether involved in abnormal metabolism ferroptosis during CAG pathogenesis. Methods: Non-atrophic (NAG) patient pathology slides were collected, related protein expression detected by immunohistochemical staining. rat model established using MNNG combined with irregular diet. Results: patients rats exhibited deposition tissue. CAG-induced the stomach characterized decreased GPX4 FTH levels increased 4-HNE levels. Hepcidin, which mainly located parietal cells, elevated high level inhibited absorption duodenum decreasing DMT1 FPN1. In addition, IL-6/STAT3 signaling pathway induced production Conclusion: Our results showed that but also intestines. Inhibiting might be new strategy for prevention future.

Language: Английский

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Nanomaterials as Theranostic Agents for Cancer Therapy

ACS Applied Nano Materials, Journal Year: 2023, Volume and Issue: 6(23), P. 21462 - 21495

Published: Nov. 29, 2023

The concept of theranostics is ground breaking in the area cancer remedy due to its capability integrate both therapeutic and diagnostic elements a single approach. This approach advantageous diagnose assess treatment simultaneously enabling identification optimum course. process includes real-time monitoring strategies through simultaneous delivery imaging agents. Nanocarriers or nanomaterials play vital role theranostic applications therapy. dual task provides various challenges. Imaging modalities are engineered enhance signal-to noise ratios while being rapidly eliminated. high-concentration accumulation curatives at site disease biocompatibility nanocarriers two important concerns considered for design nanostructures. Various have been integrated with other materials form composite efficacy along diagnosing ability. In this report, overview metal, ceramic, polymer, small-molecule-based nanoparticulate systems presented applications.

Language: Английский

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Iron chelators: as therapeutic agents in diseases

Annals of Medicine and Surgery, Journal Year: 2024, Volume and Issue: 86(5), P. 2759 - 2776

Published: March 18, 2024

The concentration of iron is tightly regulated, making it an essential element. Various cellular processes in the body rely on iron, such as oxygen sensing, transport, electron transfer, and DNA synthesis. Iron excess can be toxic because participates redox reactions that catalyze production reactive species elevate oxidative stress. chelators are chemically diverse; they coordinate six ligands octagonal sequence. Because ability to trap metals, including may involved diseases caused by stress, infectious diseases, cardiovascular neurodegenerative cancer. Iron-chelating agents, binding prohibit from functioning a catalyst transfer excrete body. Thus, use therapeutic agents has received increasing attention. This review investigates function various treating overload different clinical conditions.

Language: Английский

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