Apelin deficiency exacerbates cardiac injury following infarction by accelerating cardiomyocyte ferroptosis DOI Creative Commons

Yuechu Zhao,

Xiaoting Liang,

Ting Li

et al.

Free Radical Research, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: Dec. 28, 2024

Apelin is an endogenous ligand for the receptor and a critical protective effector in myocardial infarction (MI). Nevertheless, these mechanisms are not fully understood. Ferroptosis major driving factor of MI. This study aimed to investigate effects underlying regulatory on cardiomyocyte ferroptosis A model MI was induced adult C57BL/6J wild type (WT) knockout (Apelin−/−) mice. Cardiac function examined by echocardiography 4 weeks post-MI. RNA-seq, histochemical analyses, Western blotting were applied examine transcriptome pathological remodeling following molecular mechanisms. Mice neonatal cardiomyocytes (NCMs) used establish serum deprivation/hypoxia (SD/H) vitro. Compared with WT mice, Apelin−/− mice exhibited more severe impairment cardiac increased fibrosis infarction. Transcriptome biochemical analyses revealed involvement mediating Ferroptosis-related proteins significantly post-MI whereas p-AMPK greatly decreased. treatment activated AMPK pathway thereby inhibited NCMs SD/H These partially reversed inhibitor. deficiency aggravated dysfunction activating via inhibition pathway. offers novel potential therapeutic target treatment.

Language: Английский

Epigenetic Regulation of EMP/EMT-Dependent Fibrosis DOI Open Access
Margherita Sisto, Sabrina Lisi

Published: Jan. 3, 2024

Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often the evolution pathological conditions, causes organ failure, and can, in extreme cases, compromises functionality organs to point causing death. In recent years, considerable efforts have been made understand molecular mechanisms underlying fibrotic identify possible therapeutic strategies. Great interest has aroused discovery association between epithelial mesenchymal plasticity (EMP), particular transition (EMT), fibrogenesis, which led identification complex closely interconnected with each other, could explain EMT-dependent fibrosis. However, result remains unsatisfactory from view. advances epigenetics, is based on chromatin remodeling through various histone modifications or intervention non-coding RNAs (ncRNAs), provided more information process, this represent promising path forward for innovative strategies review, we summarize current research epigenetic involved fibrosis, focus regulation EMP/EMT-dependent

Language: Английский

Citations

4
Epigenetic regulation and post-translational modifications of ferroptosis-related factors in cardiovascular diseases DOI Creative Commons

Chenchen Jing,

Yupeng Wu, Yuzhu Zhang

et al.

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 11, 2025

As an important element of the human body, iron participates in numerous physiological and biochemical reactions. In past decade, ferroptosis (a form iron-dependent regulated cell death) has been reported to contribute pathogenesis progression various diseases. The stability cardiomyocytes is crucial for maintenance normal cardiac activity. Ferroptosis detected many cardiovascular diseases (CVDs), including coronary heart disease, myocardial ischemia–reperfusion injury, failure, chemotherapy-induced damage. cardiomyocytes, epigenetic regulation post-translational modifications regulate expression ferroptosis-related factors, maintain homeostasis, participate CVDs. Currently, there no detailed mechanism explain relationship between this review, we provide initial summary core mechanisms with first focus on factors context common We anticipate that new insights into CVDs provided here will inspire development clinical interventions specifically target active sites these reducing harmfulness health.

Language: Английский

Citations

0
VEGF-B/NRP1 Signaling Modulates Mitochondrial Homeostasis and Cardiac Function After Myocardial Infarction DOI Creative Commons

Sai Manasa Varanasi,

Ankit Sabharwal,

Riya Kar

et al.

Published: April 20, 2025

Abstract Background Myocardial infarction (MI) remains a leading cause of mortality worldwide. Recent studies suggest cardioprotective role for vascular endothelial growth factor-B (VEGF-B) in MI. However, the molecular mechanisms VEGF-B-mediated signaling via its co-receptor Neuropilin-1 (NRP1) MI are poorly understood. In this study, we investigated intricate involving VEGF-B and NRP1 cardiomyocytes (CMs) using ischemic injury as model And secondly, further validated protective VEFG-B heart disease, shedding light on their roles not only cardiac function but also therapeutic potential. Methods utilized both vitro vivo approaches to elucidate how it manifests mitochondrial functions regeneration following injury. We used two different cardiomyocyte cell lines, H9c2 (rat ventricular cardiomyocytes) HL-1 (mouse cardiomyocytes), induced hypoxia conditions, either 1% oxygen or 200µM cobalt chloride (CoCl 2 ) mimic myocardial infarction-induced heart. addition, developed novel heat shock inducible zebrafish cardiomyocyte-specific overexpression system examine . Results Our findings indicate that predominantly expressed tissue compared other tissues, expression is altered response hypoxia/ischemic results demonstrate treatment prior enhances survival, while knockdown abolishes effect, highlighting prominent cardio protection. Furthermore, found promotes survival by improving function, evidenced reduced oxidative stress ROS accumulation, decreased stress, preserved membrane potential, increased ATP levels. Lastly, our transgenic model, demonstrated protects from an NRP1-dependent manner. Conclusion study has uncovered important VEGF-B-NRP1 axis mediated beneficial CMs. Importantly, against Novelty Significance What Is Known? dysfunction, death, adverse remodeling. Vascular Endothelial Growth Factor B traditionally associated with metabolism, biology, particularly angiogenesis lipid metabolism. The neurophilin-1 receptor, VEGF-B, implicated pathways. Emerging evidence suggests may influence integrity under conditions. New Information Does This Article Contribute? exerts effect mitocondria preserving reducing stress. receptor key mediator modulates homeostasis cardiomyocytes. can attenuate apoptosis enhance bioenergetics post-MI, suggesting mechanism. Clinical Implication: These strategies aimed at enhancing VEGF-B/NRP1 improve recovery after MI, offering avenue limiting failure progression disease.

Language: Английский

Citations

0
Targeting ferroptosis offers therapy choice in sepsis-associated acute lung injury DOI
Yu Wang, Weixue Wang, Yi Zhang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117152 - 117152

Published: Dec. 8, 2024

Language: Английский

Citations

2
Epigenetic Regulation of EMP/EMT-Dependent Fibrosis DOI Open Access
Margherita Sisto, Sabrina Lisi

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2775 - 2775

Published: Feb. 28, 2024

Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often the evolution pathological conditions, causes organ failure, and can, in extreme cases, compromise functionality organs to point causing death. In recent years, considerable efforts have been made understand molecular mechanisms underlying fibrotic identify possible therapeutic strategies. Great interest has aroused discovery association between epithelial mesenchymal plasticity (EMP), particular transition (EMT), fibrogenesis, which led identification complex closely interconnected with each other, could explain EMT-dependent fibrosis. However, result remains unsatisfactory from view. advances epigenetics, based on chromatin remodeling through various histone modifications or intervention non-coding RNAs (ncRNAs), provided more information process, this represent promising path forward for innovative strategies review, we summarize current research epigenetic involved fibrosis, focus regulation EMP/EMT-dependent

Language: Английский

Citations

1
Dysregulation of long non-coding RNAs in Takayasu arteritis: A proof-of-concept study DOI
Fernanda Espinosa-Bautista, Ma. Isabel Salazar, Malinalli Brianza-Padilla

et al.

Clinical Rheumatology, Journal Year: 2024, Volume and Issue: 43(3), P. 1253 - 1259

Published: Jan. 29, 2024

Language: Английский

Citations

0
Ferroptosis exacerbates myocardial ischemia-reperfusion injury via worsening oxidative stress and inflammatory responses: the role of Ferritin/SLC7A11/GPX-4 signaling pathway DOI
Lihong Wang, Dongfang Li,

Jia Zhi

et al.

Published: Oct. 24, 2024

Abstract Ferroptosis is closely linked to pathological processes in cardiomyocytes. However, the role of ferroptosis myocardial ischemia-reperfusion injury (MI/RI) and its underlying mechanisms are unknown. Transitional accumulation iron ions, as well oxidative stress lipid peroxidation production were found MI/RI model. These significantly inhibited by an death inhibitor. In MI/RI-induced tissue damage inflammatory responses, inhibition reduced cardiac infarct area resisted inflammation. Mechanistic investigations show that via Ferritin/SLC7A11/GPX-4 axis can target mitigation, highlighting potential inhibiting a novel strategy for therapeutic MI/RI.

Language: Английский

Citations

0
Regulatory Pathways of Long Non-coding RNAs and MicroRNAs in Sepsis-Induced Cardiomyopathy: Prognostic Biomarkers and Therapeutic Targets DOI Creative Commons
Peyman Eini, Nasrin Amini,

Parsa Farzan

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract Sepsis-induced cardiomyopathy (SCM) is a life-threatening complication of sepsis, marked by temporary myocardial dysfunction. Emerging evidence highlights the critical roles long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in regulating molecular pathways involved SCM, including inflammation, oxidative stress, apoptosis. These (ncRNAs) are increasingly recognized as valuable diagnostic prognostic biomarkers, well promising therapeutic targets. This review explores potential lncRNAs miRNAs focusing on their regulatory functions applications. Key miRNAs, such miR-495 miR-21-3p, highlighted early indicators modulators disease progression. Similarly, like MALAT1 HOTAIR play crucial controlling fibrosis inflammation within myocardium. Therapeutic strategies include use miRNA mimics to restore function, antagomiRs inhibit overexpressed modulation lncRNA expression mitigate SCM Advanced delivery methods, CRISPR/Cas9 gene-editing technology, discussed innovative approaches enhance specificity efficacy ncRNA-based therapies. In conclusion, ncRNAs offer significant biomarkers agents presenting new avenues for targeted treatment. However, further research required address challenges related delivery, specificity, long-term safety clinical

Language: Английский

Citations

0
Apelin deficiency exacerbates cardiac injury following infarction by accelerating cardiomyocyte ferroptosis DOI Creative Commons

Yuechu Zhao,

Xiaoting Liang,

Ting Li

et al.

Free Radical Research, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: Dec. 28, 2024

Apelin is an endogenous ligand for the receptor and a critical protective effector in myocardial infarction (MI). Nevertheless, these mechanisms are not fully understood. Ferroptosis major driving factor of MI. This study aimed to investigate effects underlying regulatory on cardiomyocyte ferroptosis A model MI was induced adult C57BL/6J wild type (WT) knockout (Apelin−/−) mice. Cardiac function examined by echocardiography 4 weeks post-MI. RNA-seq, histochemical analyses, Western blotting were applied examine transcriptome pathological remodeling following molecular mechanisms. Mice neonatal cardiomyocytes (NCMs) used establish serum deprivation/hypoxia (SD/H) vitro. Compared with WT mice, Apelin−/− mice exhibited more severe impairment cardiac increased fibrosis infarction. Transcriptome biochemical analyses revealed involvement mediating Ferroptosis-related proteins significantly post-MI whereas p-AMPK greatly decreased. treatment activated AMPK pathway thereby inhibited NCMs SD/H These partially reversed inhibitor. deficiency aggravated dysfunction activating via inhibition pathway. offers novel potential therapeutic target treatment.

Language: Английский

Citations

0