TSAT-Urated Insights: Clarifying the Complexities of Hereditary Hemochromatosis and Its Guidelines DOI Creative Commons

Chiara Marcon,

Marta Medeot,

A. Michelazzi

et al.

Hemato, Journal Year: 2024, Volume and Issue: 5(4), P. 459 - 489

Published: Dec. 11, 2024

Hereditary hemochromatosis (HH) related to HFE-gene mutations is a well-known condition, yet its understanding remains complex. The BIOIRON classification emphasizes that only homozygosity for the C282Y mutation should be considered pathogenic. penetrance of HFE-related HH highly variable. Symptoms are often challenging recognize at time presentation, and systemic involvement may overlap with other diseases. Hyperferritinemia elevated transferrin saturation levels still milestones in diagnosis, but they also common findings many clinical conditions. Furthermore, current diagnostic therapeutic guidelines not always unequivocal defining patients’ characteristics, as well treatment management goals. Our work provides concise overview latest evidence regarding pathogenic mechanisms, picture, differential diagnosis tools. Alongside this, it summarizes compares main recommendations from principal issued by 2017 Hemochromatosis International Meeting, American College Gastroenterology, European Association Study Liver, Molecular Genetics Quality Network, DUTCH guidelines, British Society Haematology. Summarizing tables quick consultation provided.

Language: Английский

The mechanisms of ferroptosis and its role in atherosclerosis DOI Open Access

Xi Xu,

Xiaodan Xu, Mengqing Ma

et al.

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

Citations

43

Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications DOI Open Access
George J. Kontoghiorghes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12928 - 12928

Published: Aug. 18, 2023

Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions patients, including those with overload other forms toxicity. Excess load an adverse prognostic factor diseases can cause serious organ damage fatalities following chronic red blood cell transfusions in patients many conditions, hemoglobinopathies, myelodyspasia, hematopoietic stem transplantation. Similar toxicity excess body but at a slower rate disease progression found idiopathic haemochromatosis patients. deposition different regions the brain suspected has been identified by MRI T2* similar methods neurodegenerative diseases, Alzheimer’s Parkinson’s disease. Based on its role as major biological catalyst free radical reactions Fenton reaction, also implicated associated pathology tissue damage. Furthermore, recent discovery ferroptosis, which death program based generation membrane lipid oxidation, sparked thousands investigations association cardiac, kidney, liver, cancer infections. The implications labile, non-protein bound form complexes dietary molecules such vitamin C drugs doxorubicin xenobiotic relation to carcinogenesis are discussed. In each case toxicity, mechanistic insights, diagnostic criteria, molecular interactions design new effective therapeutic interventions future targeted strategies. particular, this approach successful treatment most loading conditions especially transition thalassemia from fatal due protocols resulting complete elimination

Language: Английский

Citations

30

Targeting ferroptosis: a new therapeutic opportunity for kidney diseases DOI Creative Commons
Zhiyong Long,

Yanfang Luo,

Min Yu

et al.

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

Published: July 3, 2024

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and characterized by the accumulation lipid peroxides to lethal levels. involves multiple pathways including redox balance, regulation, mitochondrial function, amino acid, lipid, glycometabolism. Furthermore, various disease-related signaling also play role in regulating process oxidation. In recent years, with emergence concept ferroptosis in-depth study its mechanisms, closely associated biological conditions related kidney diseases, organ development, aging, immunity, cancer. This article reviews development ferroptosis, mechanisms (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, MBOAT1/2 pathways), latest research progress involvement diseases. It summarizes diseases within frameworks metabolism, reactive oxygen biology, biology. The introduces key regulatory factors as well important concepts major open questions natural compounds. hoped future research, further breakthroughs can be made understanding regulation mechanism utilizing promote treatments for such acute injury(AKI), chronic disease (CKD), diabetic nephropathy(DN), renal carcinoma. paves way new approach prevent, treat clinical

Language: Английский

Citations

10

A novel mechanism of ferroptosis inhibition‐enhanced atherosclerotic plaque stability: YAP1 suppresses vascular smooth muscle cell ferroptosis through GLS1 DOI
Yanyu Chen, Yuting Cui, Man Li

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(15)

Published: Aug. 2, 2024

Abstract Atherosclerosis is a leading cause of cardiovascular diseases (CVDs), often resulting in major adverse events (MACEs), such as myocardial infarction and stroke due to the rupture or erosion vulnerable plaques. Ferroptosis, an iron‐dependent form cell death, has been implicated development atherosclerosis. Despite its involvement CVDs, specific role ferroptosis atherosclerotic plaque stability remains unclear. In this study, we confirmed presence unstable plaques demonstrated that inhibitor ferrostatin‐1 (Fer‐1) stabilizes apolipoprotein E knockout ( Apoe −/− ) mice. Using bioinformatic analysis combining RNA sequencing (RNA‐seq) with single‐cell (scRNA‐seq), identified Yes‐associated protein 1 (YAP1) potential key regulator vascular smooth muscle cells (VSMCs) vitro, found YAP1 protects against oxidized low‐density lipoprotein (oxLDL)‐induced VSMCs. Mechanistically, exerts anti‐ferroptosis effects by regulating expression glutaminase (GLS1) promote synthesis glutamate (Glu) glutathione (GSH). These findings establish novel mechanism where inhibition promotes stabilization through YAP1/GLS1 axis, attenuating VSMC ferroptosis. Thus, targeting axis suppress may represent strategy for preventing treating

Language: Английский

Citations

8

Nanomedicine-based drug delivery strategies for the treatment of atherosclerosis DOI Creative Commons

Yongfang Lin,

Ruibo Lin,

Han-bin Lin

et al.

Medicine in Drug Discovery, Journal Year: 2024, Volume and Issue: 22, P. 100189 - 100189

Published: April 5, 2024

Atherosclerosis, a highly prevalent cardiovascular disease, has significantly contributed to morbidity and mortality worldwide. Despite the availability of various treatment options in clinical practice, complete reversal atherosclerotic pathological process remains challenging. Traditional anti-arteriosclerosis drugs often suffer from poor solubility, limited targeting ability obvious adverse effects. Additionally, novel therapeutics such as genetic protein-based inherently instability issues, thereby compromising their actual curative efficacy impeding further application. Recently, nanomedicine-based drug delivery strategies have emerged promising approaches for treating atherosclerosis due specifically transport target cells, microstructures specific molecules within lesion sites. These advanced features enhance properties bioavailability while minimizing off-target Moreover, numerous studies demonstrated that nanomedicine not only inhibits plaque progression but also reduces lesional areas eventually reverses atherosclerosis. The utilization is considered an important therapeutic tactic mitigating residual risks associated with This review provides comprehensive overview emerging targeted anti-atherosclerosis drugs, elucidating distinct mechanisms highlighting remarkable combating critical challenges future perspectives development application are thoroughly discussed.

Language: Английский

Citations

5

HMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis DOI
Xiang Peng,

Bin Sun,

Chaohui Tang

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

5

Key role of the CSE/transsulfuration pathway in macrophage phenotypic change under iron overload DOI Creative Commons
Zheng Yuan, Yuxuan Chen,

Yijun Xin

et al.

Journal of Trace Elements in Medicine and Biology, Journal Year: 2025, Volume and Issue: 88, P. 127611 - 127611

Published: Feb. 3, 2025

Iron homeostasis has a significant impact on the phenotypic transformation of macrophages and is implicated in various diseases. In this study, we evaluated effect cystathionine-gamma-lyase (CSE)/transsulfuration pathway iron-overload induced macrophage phenotype change. The biochemical parameters, such as qRT-PCR, western blot, fluorescence staining, were assessed both vitro vivo. overload disrupts iron metabolism alters expression genes involved transport, resulting polarization towards M1 an alternating activation state M2. Meanwhile, excessive led to increase lipid peroxidation levels disrupted cysteine metabolism. By utilizing erastin inhibit SLC7A11 activity block exogenous uptake, able observe exacerbation proinflammatory under conditions deprivation. CSE/transsulfuration pathway, serves primary route for endogenous synthesis. presence overload, CSE was upregulated further enhanced by Deletion CSE-knockout mice exacerbated inflammatory transition iron-overloaded impacting ferritinophagy. regulated change iron-overload, which may offer novel insights into potential therapeutic strategies overload-related disorders.

Language: Английский

Citations

0

Transferrin receptors DOI Creative Commons
Qian Guo,

Christopher Qian,

Xinyu Wang

et al.

Experimental & Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

Citations

0

Repeated Injection of Very Small Superparamagnetic Iron Oxide Particles (VSOPs) in Murine Atherosclerosis: A Safety Study DOI Creative Commons
Tobias Haase, Antje Ludwig, Anke Stach

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(9), P. 773 - 773

Published: April 28, 2024

Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background pre-existing hyperlipidemia atherosclerosis has not yet studied. This study aimed to investigate effect multiple intravenous injections VSOPs atherosclerotic mice. Taurine-formulated (VSOP-T) were repeatedly intravenously injected at 100 µmol Fe/kg apolipoprotein E-deficient (ApoE KO) mice with diet-induced Angiographic was carried out by vivo MRI. Magnetic particle spectrometry used detect tissue VSOP content, content quantified photometrically. Pathological changes organs, plaque development, expression hepatic iron-related proteins evaluated. VSOP-T enabled angiographic heart blood vessels a half-life one hour. Repeated injection led deposition accumulation liver spleen without affecting pathology, metabolism proteins, serum lipids, or lesion formation. doses sufficient MRA analyses had no significant effects on burden, steatohepatitis, homeostasis These findings underscore safety support its further development agent tool.

Language: Английский

Citations

2

Rational design and comparison of two pyrimidine-based ultra-fast response fluorescent probes from 2-hydroxy-3-pinanone for monitoring Fe2+ homeostatic systems in living organisms DOI
Zheyu Shen, Yixin Yang, Shuai Gong

et al.

Microchemical Journal, Journal Year: 2023, Volume and Issue: 195, P. 109519 - 109519

Published: Oct. 15, 2023

Language: Английский

Citations

4