Comprehensive Analysis Based on Genes Associated With Cuproptosis, Ferroptosis, and Pyroptosis for the Prediction of Diagnosis and Therapies in Coronary Artery Disease

Cardiovascular Therapeutics, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Coronary artery disease (CAD) is a complex condition influenced by genetic factors, lifestyle, and other risk factors that contribute to increased mortality. This study aimed at evaluating the diagnostic potential of genes associated with cuproptosis, ferroptosis, pyroptosis (CFP) using network modularization machine learning methods. CAD‐related datasets GSE42148, GSE20680, GSE20681 were sourced from GEO database, related CFP gathered MsigDB FerrDb literature. To identify linked these pathways, weighted gene coexpression analysis (WGCNA) was used isolate modules. The accuracy key in modules then assessed LASSO, SVM, random forest models. Immunity drug sensitivity correlation analyses subsequently performed investigate possible underlying mechanisms. function gene, STK17B, analyzed through western blot transwell assays. Two strong correlations identified validated. SVM model outperformed LASSO models, demonstrating superior discriminative power (AUC = 0.997 blue module AUC 1.000 turquoise module), nine identified: CTDSP2, DHRS7, NLRP1, MARCKS, PELI1, RILPL2, JUNB, SLC40A1. Knockdown STK17B inhibited cell migration invasion human umbilical vein endothelial cells. In summary, our findings suggest hold as biomarkers therapeutic targets, playing role CAD progression.

Язык: Английский

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LncRNA MEG3 exacerbates diabetic cardiomyopathy via activating pyroptosis signaling pathway

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

Background: Diabetic cardiomyopathy (DCM) is a prevalent complication observed in diabetic patients. The long non-coding RNA maternally expressed gene 3 (lncMEG3) has been found to be intricately associated with myocardial infarction and heart failure. However, the role of lncMEG3 DCM remains unclear. present study was designed investigate elucidate underlying molecular mechanisms. Methods: mouse model established through intraperitoneal injection streptozotocin (STZ). heart-targeted adeno-associated virus carrying interfering (AAV9-shMEG3) administered via tail-vein induce silencing mice. Echocardiography performed evaluate cardiac function, while hematoxylin eosin (H&E) staining Masson trichrome were employed for detection remodeling. mechanisms investigated using Western blot real-time PCR (qPCR). Results: expression increased hearts AC16 cardiomyocytes treated high glucose. knockout reduced inflammation, fibrosis hypertrophy, improved dysfunction In mice, activation nucleotide-binding oligomerization domain-like receptor pyrin domain containing (NLRP3)-inflammasome observed, whereas resulted reduction NLRP3 inflammasome activation. Mechanistically, we discovered that specifically functions as competitive inhibitor miR-223. Moreover, use miR-223 antisense oligonucleotide (AMO) counteracted suppressive effects knockdown on induced by glucose vitro. Conclusion: LncMEG3 exacerbates enhancing attenuating miR-223-mediated degradation individuals diabetes.

Язык: Английский

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Identification and validation of pyroptosis-related genes as potential biomarkers for hypertrophic cardiomyopathy: A comprehensive bioinformatics analysis

Medicine, Год журнала: 2024, Номер 103(4), С. e36799 - e36799

Опубликована: Янв. 26, 2024

Pyroptosis plays a key role in the death of cells including cardiomyocytes, and it is associated with variety cardiovascular diseases. However, pyroptosis-related genes (PRGs) hypertrophic cardiomyopathy (HCM) not well characterized. This study aimed to identify biomarkers explore molecular mechanisms underlying functions PRGs HCM. The differentially expressed were identified by GEO2R, (DEPRGs) HCM combining PRGs. Enrichment analysis was performed using "clusterProfiler" package R software. Protein-protein interactions (PPI) network STRING database, hub screened cytoHubba. TF-miRNA coregulatory networks protein-chemical analyzed NetworkAnalyst. RT-PCR/WB used for expression validation diagnostic markers. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) Western Blot (WB) measure compare cardiac hypertrophy model control group. A total 20 DEPRGs identified, which primarily showed enrichment positive regulation cytokine production, response biotic stimulus, tumor necrosis factor other biological processes. These processes involved pathways related Renin-angiotensin system, Adipocytokine signaling pathway NF-kappa B pathway. Then, PPI constructed, 8 identified. After verification analysis, finally HCM-related markers upregulated gene protein tyrosine phosphatase non-receptor type 11 (PTPN11), downregulated interleukin-1 receptor-associated kinase 3 (IRAK3), annexin A2 (ANXA2). Further GSEA revealed these muscle contraction, cardiomyopathy, fatty acid degradation ECM - receptor interaction. Moreover, we also elucidated interaction miRNA known compounds, respectively. results indicated that PTPN11 significantly increased, IRAK3 ANXA2 expressions decreased PTPN11, IRAK3, as pyroptosis-associated HCM, potential reveal development pathogenesis could be therapeutic targets.

Язык: Английский

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Exploring the role of pyroptosis in the pathogenicity of heart disease

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Апрель 5, 2024

Cell death is an essential cellular mechanism that ensures quality control and whole-body homeostasis. Various modes of cell have been studied detailed. Unbalanced can lead to uncontrolled proliferation (i.e., tumors) or excessive loss cells ischemia injury tissue loss). Thus, it imperative for be balanced controlled. Here, we will focus on a recent mode called pyroptosis. While extensive studies shown the role this route in macrophages monocytes, evidence pyroptosis expanded encompass other pathologies, including cancer cardiac diseases. Herein, provide brief review discuss current gaps knowledge scientific advances years. Lastly, conclusions prospective relevance various

Язык: Английский

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Therapeutic implications of targeting pyroptosis in Cardiac-related etiology of heart failure

Biochemical Pharmacology, Год журнала: 2022, Номер 204, С. 115235 - 115235

Опубликована: Авг. 28, 2022

Язык: Английский

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Sex-Dependent Mechanisms of Cell Death Modalities in Cardiovascular Disease

Canadian Journal of Cardiology, Год журнала: 2022, Номер 38(12), С. 1844 - 1853

Опубликована: Сен. 21, 2022

Язык: Английский

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Bioactive Molecules against Rheumatoid Arthritis by Suppressing Pyroptosis

Pharmaceuticals, Год журнала: 2023, Номер 16(7), С. 952 - 952

Опубликована: Июль 3, 2023

Rheumatoid arthritis is an inflammatory disease, and pyroptosis a form of death associated with response. Pyroptosis, which occurs in synovial osteoblastic cells, can exacerbate the development rheumatoid arthritis. The inhibition these cells can, therefore, clearly be used as therapeutic strategy against Here, we have summarized current status progress treatment by targeting cellular pyroptosis. We identified seven compounds, including cyclic RNA, microRNA, peptide, cytokine (protein), that may influence progression regulating initiation All compounds been shown to anti-rheumatoid effects vitro and/or vivo potential developed agents. These findings help accelerate drugs.

Язык: Английский

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Investigating the NF-κB Signaling Pathway in Heart Failure: Exploring Potential Therapeutic Approaches

Heliyon, Год журнала: 2024, Номер 10(23), С. e40812 - e40812

Опубликована: Ноя. 30, 2024

Язык: Английский

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Inhibition of Sema4D attenuates pressure overload-induced pathological myocardial hypertrophy via the MAPK/NF-κB/NLRP3 pathways

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2023, Номер 1870(3), С. 166944 - 166944

Опубликована: Ноя. 10, 2023

Язык: Английский

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Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 23, 2022

Introduction Extracellular matrix turnover, a ubiquitous dynamic biological process, can be diverted to fibrosis. The latter affect the intestine as serious complication of Inflammatory Bowel Diseases (IBD) and is resistant current pharmacological interventions. It embosses need for out-of-the-box approaches identify target molecular mechanisms Methods results In this study, novel mRNA sequencing dataset 22 pairs intestinal biopsies from terminal ileum (TI) sigmoid 7 patients with Crohn’s disease, 6 ulcerative colitis 9 control individuals (CI) served validation cohort core fibrotic transcriptomic signature (FIBSig), This signature, which was identified in publicly available data (839 samples healthy individuals) 5 disorders affecting different organs (GI tract, lung, skin, liver, kidney), encompasses 241 genes functional pathways derive their interactome. These were used further bioinformatics co-expression analyses elucidate site-specific background fibrosis highlighting involvement, particularly ileum. We also confirmed profiles our cohort. Combining these we highlight 21 hub within larger single module, highly enriched CD patients. Further pathway analysis revealed known inflammation-regulated, fibrogenic operating TI, such IL-13 signaling pyroptosis, respectively. Discussion findings provide rationale increased incidence at future evaluation mechanistic translational studies.

Язык: Английский

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