Epigenetics in Heart Failure DOI Open Access
Jamie Sin Ying Ho,

Eric Jou,

Pek‐Lan Khong

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12010 - 12010

Published: Nov. 8, 2024

Heart failure is a clinical syndrome with rising global incidence and poor prognosis despite improvements in medical therapy. There increasing research interest epigenetic therapies for heart failure. Pathological cardiac remodelling may be driven by stress-activated signalling cascades, emerging has shown the involvement of signals that regulate transcriptional changes leading to In this review, we appraise current evidence role modifications These include DNA methylation histone methylation, acetylation, phosphorylation, ubiquitination sumoylation, which are critical processes establish an pattern translate environmental stress into genetic expression, remodeling. We summarize potential currently development, including limited trials The dynamic epigenome disease process require further elucidation, so does impact on development therapeutics. Understanding epigenetics pave way identification novel biomarkers molecular targets, facilitate personalized important condition.

Language: Английский

An integrated view of lipid metabolism in ferroptosis revisited via lipidomic analysis DOI Creative Commons
Jong Woo Kim, Ji-Yoon Lee,

Mihee Oh

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(8), P. 1620 - 1631

Published: Aug. 23, 2023

Abstract Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular neurodegeneration, liver disease, cancer. Although polyunsaturated fatty acids (PUFAs) membrane phospholipids are preferentially oxidized, saturated/monounsaturated (SFAs/MUFAs) also influence peroxidation ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs PUFAs they control acid pools via uptake β-oxidation, impacting Furthermore, discuss stored different lipids, diacyl or ether with head groups; triglycerides; cholesterols. Moreover, these released from molecules. summary, provide an integrated view the diverse dynamic metabolic processes context ferroptosis revisiting lipidomic studies. Thus, review development therapeutic strategies for ferroptosis-related diseases.

Language: Английский

Citations

55
Ferroptosis inhibitors: past, present and future DOI Creative Commons
Lei Zhang, Yi Luo, Yang Xiang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 23, 2024

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed mechanisms its formation continue to explore effective inhibitors in disease. Recent studies shown correlation between pathological neurodegenerative diseases, as well diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for treatment ferroptosis-mediated diseases. This article specifically describes metabolic pathways summarizes reported action natural synthetic small molecule their efficacy The paper also treatments such gene therapy, nanotechnology, summarises challenges encountered clinical translation inhibitors. Finally, relationship other modes discussed, hopefully paving way future drug design discovery.

Language: Английский

Citations

20
DOXORUBICIN-RELATED CARDIOTOXICITY: REVIEW OF FUNDAMENTAL PATHWAYS OF CARDIOVASCULAR SYSTEM INJURY DOI
Ashot Avagimyan, Nana Pogosova, L. V. Kakturskiy

et al.

Cardiovascular Pathology, Journal Year: 2024, Volume and Issue: 73, P. 107683 - 107683

Published: Aug. 6, 2024

Language: Английский

Citations

17
Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis DOI
Xingli Zhang,

Jing Shi,

Ruonan Wang

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 471, P. 134389 - 134389

Published: April 23, 2024

Language: Английский

Citations

9
Mitochondrial quality control: Biochemical mechanism of cardiovascular disease DOI Creative Commons

Francesca Inferrera,

Ylenia Marino,

Tiziana Genovese

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2025, Volume and Issue: 1872(3), P. 119906 - 119906

Published: Jan. 19, 2025

Language: Английский

Citations

1
Dietary Trace Elements and the Pathogenesis of Neurodegenerative Diseases DOI Open Access
Masahiro Kawahara,

Midori Kato‐Negishi,

Ken‐ichiro Tanaka

et al.

Nutrients, Journal Year: 2023, Volume and Issue: 15(9), P. 2067 - 2067

Published: April 25, 2023

Trace elements such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) are absorbed from food via the gastrointestinal tract, transported into brain, play central roles in normal brain functions. An excess of these trace often produces reactive oxygen species damages brain. Moreover, increasing evidence suggests that dyshomeostasis metals is involved pathogenesis neurodegenerative diseases, including Alzheimer’s disease, prion Lewy body diseases. The disease-related amyloidogenic proteins can regulate metal homeostasis at synapses, thus loss protective functions causes neurodegeneration. Meanwhile, metal-induced conformational changes contribute to enhancing their neurotoxicity. Zn Cu vascular-type senile dementia. Here, we present an overview intake, absorption, transport four essential (Fe, Zn, Cu, Mn) one non-essential element (aluminum: Al) connections with diseases based on metal–protein, metal–metal cross-talk.

Language: Английский

Citations

17
Sodium-glucose cotransporter 2 inhibitors induce anti-inflammatory and anti-ferroptotic shift in epicardial adipose tissue of subjects with severe heart failure DOI Creative Commons
Barbora Judita Kasperová, Miloš Mráz, Petr Svoboda

et al.

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

Published: June 28, 2024

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type diabetes mellitus, which also improve heart failure and decrease risk cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute development failure. We aimed elucidate a possible role changes in EAT metabolic inflammatory profile beneficial cardioprotective effects SGLT-2i subjects with severe Methods 26 failure, reduced ejection fraction, treated versus without treatment, matched age (54.0 ± 2.1 vs. 55.3 years, n.s.), body mass index (27.8 0.9 28.8 1.0 kg/m , n.s.) left ventricular fraction (20.7 0.5 23.2 1.7%, who were scheduled transplantation or mechanical support implantation, included study. A complex metabolomic gene expression analysis obtained during surgery performed. Results ameliorated inflammation, as evidenced by improved pro-inflammatory genes decreased infiltration immune cells into EAT. Enrichment ether lipids oleic acid noted on suggests disposition ferroptosis, potentially further contributing oxidative stress subjects. Conclusions Our results show inflammation patients SGLT-2i, compared this therapy. Modulation status could represent novel mechanism behind SGLT-2i-associated

Language: Английский

Citations

8
Iron Metabolism in Cancer and Senescence: A Cellular Perspective DOI Creative Commons
Elvira Crescenzi, Antonio Leonardi, Francesco Pacifico

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(7), P. 989 - 989

Published: July 11, 2023

Iron participates in a number of biological processes and plays crucial role cellular homeostasis. Alterations iron metabolism are considered hallmarks cancer drivers aggressive behaviors, such as uncontrolled proliferation, resistance to apoptosis, enhanced metastatic ability, increased cell plasticity stemness. Furthermore, dysregulated has been associated with the development an adverse tumor microenvironment. have described senescence aging. For instance, shown accumulate aged tissues age-related diseases. vitro studies demonstrate increases content both replicative stress-induced senescent cells. However, role, mechanisms regulation dysregulation effects on remain significantly less characterized. In this review, we first provide overview regulatory proteins. Then, summarize alterations homeostasis from point view.

Language: Английский

Citations

12
Klf6 aggravates myocardial ischemia/reperfusion injury by activating Acsl4‐mediated ferroptosis DOI Creative Commons

Mali Qiu,

Wei Yan,

M. Liu

et al.

The Kaohsiung Journal of Medical Sciences, Journal Year: 2023, Volume and Issue: 39(10), P. 989 - 1001

Published: Aug. 2, 2023

Abstract Ferroptosis is closely related to myocardial ischemia/reperfusion (I/R) damage. Kruppel‐like factor 6 (Klf6) can aggravate renal I/R injury. We aimed elucidate the role of Klf6 in damage as well its potential mechanism. Myocardial mice model and hypoxia/reoxygenation (H/R)‐treated HL‐1 cells were established. The levels Fe 2+ , MDA, lipid ROS, ferroptosis‐related proteins measured for assessing ferroptosis. Infarct area, H&E staining, cardiac function, cell viability detected evaluating Immunohistochemistry, immunofluorescence, western blot, RT‐qPCR applied detecting genes. m6A modification Klf6, relationships between Mettl3, Igf2bp2, or Acsl4 promoter, was evaluated using MeRIP, RNA immunoprecipitation, pull‐down, chromatin luciferase reporter assay accordingly.Klf6 protein mRNA levels, modification, elevated subjected H/R heart tissues from mice. In H/R‐challenged cells, binding Igf2bp2 Mettl3 confirmed; moreover, knockdown decreased level inhibited stability. restrained H/R‐triggered loss, improved I/R‐induced injury, ferroptosis models. directly bound promoter positively regulated expression. overexpression compromised knockdown‐generated protective effect cells.m6A modification‐regulated aggravated through activating Acsl4‐mediated ferroptosis, thereby providing one target treatment I/R.

Language: Английский

Citations

12
The Cellular Stability Hypothesis: Evidence of Ferroptosis and Accelerated Aging-Associated Diseases as Newly Identified Nutritional Pentadecanoic Acid (C15:0) Deficiency Syndrome DOI Creative Commons
Stephanie Venn‐Watson

Metabolites, Journal Year: 2024, Volume and Issue: 14(7), P. 355 - 355

Published: June 23, 2024

Ferroptosis is a newly discovered form of cell death caused by the peroxidation fragile fatty acids in membranes, which combines with iron to increase reactive oxygen species and disable mitochondria. has been linked aging-related conditions, including type 2 diabetes, cardiovascular disease, nonalcoholic liver disease (NAFLD). Pentadecanoic acid (C15:0), an odd-chain saturated fat, essential primary roles stabilizing membranes repairing mitochondrial function. By doing so, C15:0 reverses underpinnings ferroptosis. Under proposed “Cellular Stability Hypothesis”, evidence provided show that optimally need >0.4% 0.64% support long-term health longevity. A pathophysiology identified nutritional deficiency syndrome (“Cellular Fragility Syndrome”) demonstrates how deficiencies (≤0.2% total circulating acids) can susceptibilities ferroptosis, dysmetabolic overload syndrome, NAFLD. Further, supplementation reverse described key components Given declining dietary intake C15:0, especially among younger generations, there for extensive studies understand potential breadth Cellular Syndrome across populations.

Language: Английский

Citations

4