Identification of novel key genes and signaling pathways in hypertrophic cardiomyopathy: evidence from bioinformatics and next generation sequencing data analysis DOI Open Access
Basavaraj Vastrad, Chanabasayya Vastrad

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Hypertrophic cardiomyopathy (HCM) is a global health problem characterized by left ventricle become thick and stiff with effect of indication including chest pain, fluttering, fainting shortness breath. In this investigation, we aimed to identify diagnostic markers analyzed the therapeutic potential essential genes. Next generation sequencing (NGS) dataset GSE180313 was obtained from Gene Expression Omnibus (GEO) database used differentially expressed genes (DEGs) in HCM. DEGs were screened using DESeq2 Rbioconductor tool. Then, Ontology (GO) REACTOME pathway enrichment analyses performed. Moreover, protein-protein interaction (PPI) network constructed, module analysis Next, miRNA-hub gene regulatory TF-hub constructed analyzed. Finally, values hub assessed receiver operating characteristic (ROC) curve analysis. By performing analysis, total 958 (479 up regulated 479 down genes) successfully identified GSE180313, respectively. GO revealed that functions signaling pathways significantly enriched response stimulus, multicellular organismal process, metabolism extracellular matrix organization. The FN1, SOX2, TUBA4A, RPS2, TUBA1C, ESR1, SNCA, LCK, PAK1 APLNR might be associated gens FN1 TPM3, together corresponding predicted miRNAs (e.g., hsa-mir-374a-5p hsa-miR-8052), SH3KBP1 ESR1 TFs (e.g PRRX2 STAT3) found correlated This investigation could serve as basis for further understanding molecular pathogenesis targets

Language: Английский

Ferroptosis mechanisms and regulations in cardiovascular diseases in the past, present, and future DOI Creative Commons

Wenxi Fang,

Saiyang Xie, Wei Deng

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: March 21, 2024

Abstract Cardiovascular diseases (CVDs) are the main that endanger human health, and their risk factors contribute to high morbidity a rate of hospitalization. Cell death is most important pathophysiology in CVDs. As one cell mechanisms, ferroptosis new form regulated (RCD) broadly participates CVDs (such as myocardial infarction, heart transplantation, atherosclerosis, failure, ischaemia/reperfusion (I/R) injury, atrial fibrillation, cardiomyopathy (radiation-induced cardiomyopathy, diabetes sepsis-induced cardiac doxorubicin-induced iron overload hypertrophic cardiomyopathy), pulmonary arterial hypertension), involving regulation, metabolic mechanism lipid peroxidation. This article reviews recent research on regulation its relationship with occurrence treatment CVDs, aiming provide ideas targets for clinical diagnosis by clarifying latest progress research. Graphical • The identification, development history characterization ferroptosis. role different subcellular organelles organelle-specific regulators includes metabolism, amino acid metabolism. cardiovascular cells diseases. efficacy pathological involved

Language: Английский

Citations

22
Ferroptosis Mediated Inflammation Promotes Pulmonary Hypertension DOI
Felipe Kazmirczak,

Neal T. Vogel,

Sasha Z. Prisco

et al.

Circulation Research, Journal Year: 2024, Volume and Issue: 135(11), P. 1067 - 1083

Published: Oct. 18, 2024

Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in peroxidation ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation macrophage recruitment. In pulmonary arterial hypertension (PAH), endothelial cells exhibit cellular phenotypes promote Moreover, there ectopic deposition accumulation the vasculature. However, effects ferroptosis inhibition on these pathogenic mechanisms landscape vasculature are incompletely defined.

Language: Английский

Citations

9
LncRNA MIR210HG promotes phenotype switching of pulmonary arterial smooth muscle cells through autophagy-dependent ferroptosis pathway DOI
Enze Wang, Binbin Zhang, Ling Huang

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(9-10), P. 1648 - 1662

Published: April 18, 2024

Language: Английский

Citations

7
Exploring the inflammation-related mechanisms of Lingguizhugan decoction on right ventricular remodeling secondary to pulmonary arterial hypertension based on integrated strategy using UPLC-HRMS, systems biology approach, and experimental validation DOI
Jiayu Lv,

Shuqing Shi,

Zhenyue Fu

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 132, P. 155879 - 155879

Published: July 14, 2024

Language: Английский

Citations

3
Panorama of artery endothelial cell dysfunction in pulmonary arterial hypertension DOI
Yuhui Shen,

Dong Ding,

Tian‐Yu Lian

et al.

Journal of Molecular and Cellular Cardiology, Journal Year: 2024, Volume and Issue: 197, P. 61 - 77

Published: Oct. 20, 2024

Language: Английский

Citations

2
Ferroptosis Promotes Pulmonary Hypertension DOI Creative Commons
Felipe Kazmirczak,

Neal T. Vogel,

Sasha Z. Prisco

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 20, 2023

Abstract Background Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species (ROS) generation, results in peroxidation ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation macrophage recruitment. In pulmonary arterial hypertension (PAH), endothelial cells (PAEC) exhibit cellular phenotypes promote Moreover, there ectopic deposition accumulation the vasculature. However, effects ferroptosis inhibition on these pathogenic mechanisms landscape vasculature are incompletely defined. Methods Multi-omics physiological analyses evaluated how modulated preclinical PAH. The impact AAV1-mediated expression pro-ferroptotic protein ACSL4 PAH was determined, a genetic association study humans further probed relationship between (PH). Results Ferrostatin-1, small-molecule inhibitor, mitigated severity monocrotaline rats. RNA-seq proteomics demonstrated associated with severity. RNA-seq, proteomics, confocal microscopy revealed pro-inflammatory cytokines/chemokines were suppressed ferrostatin-1. Additionally, ferrostatin-1 combatted changes endothelial, smooth muscle, interstitial abundance gene patterns as deconvolution RNA-seq. Ferroptotic PAEC damage molecular restructured transcriptomic signature, mitochondrial morphology, promoted proliferation artery muscle cells, created phenotype monocytes vitro . AAV1- Acsl4 induced Finally, single-nucleotide polymorphisms six genes identified potential link PH Vanderbilt BioVU repository. Conclusions through metabolic

Language: Английский

Citations

5
The Therapeutic Potential of Targeting Ferroptosis in the Treatment of Mitochondrial Cardiomyopathies and Heart Failure DOI
Aubrey C. Cantrell,

Heng Zeng,

Jian‐Xiong Chen

et al.

Journal of Cardiovascular Pharmacology, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 10, 2023

Ferroptosis is a form of iron-regulated cell death implicated in wide array diseases, including heart failure, hypertension, and numerous cardiomyopathies. In addition, mitochondrial dysfunction has been associated with several these same disease states. However, the role mitochondrion ferroptotic remains debated. As major regulator cellular iron levels, mitochondria may very well play crucial mechanisms behind ferroptosis, but at this point, not adequately defined. Emerging evidence from our laboratory others indicates critical Sirtuin 3, deacetylase linked longevity protection against conditions, prevention cardiovascular diseases. Here, we provide brief overview potential roles 3 homeostasis its contribution to cardiomyopathy Friedreich's ataxia diabetic cardiomyopathy. We also discuss current knowledge involvement ferroptosis other states, doxorubicin-induced cardiomyopathy, insight into areas requiring further investigation.

Language: Английский

Citations

5
Metabolic Reprogramming in Cardiovascular Diseases DOI Open Access
Juan Gao,

Yujiao Zhu,

Yihua Bei

et al.

Journal of Cardiovascular Translational Research, Journal Year: 2024, Volume and Issue: 17(1), P. 33 - 35

Published: Feb. 1, 2024

Language: Английский

Citations

1
Coenzyme Q10 Alleviates Silicosis FibrosisviaInhibiting Ferroptosis in Mice DOI Open Access
Yue Sun, Mengxue Yu, H. Zhang

et al.

In Vivo, Journal Year: 2024, Volume and Issue: 39(1), P. 180 - 189

Published: Dec. 31, 2024

Silicosis, the most severe type of occupational pneumoconiosis, leads to diffuse pulmonary fibrosis without specific therapy. Ferroptosis is triggered by reactive oxygen species (ROS) and Fe

Language: Английский

Citations

1
Ferroptosis Inhibition Combats Metabolic Derangements and Improves Cardiac Function in Pulmonary Artery Banded Pigs DOI Creative Commons
Felipe Kazmirczak,

Ryan Moon,

Neal T. Vogel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 26, 2024

Abstract Right heart failure (RHF) is a leading cause of mortality in multiple cardiovascular diseases and preclinical human data suggest impaired metabolism significant contributor to right-sided cardiac dysfunction. Ferroptosis nonapopotic form cell death driven by metabolism. Rodent suggests ferroptosis inhibition can restore mitochondrial electron transport chain function enhance contractility left models, but the effects translational large animal models RHF are unknown. Here, we showed ferrostatin-1 mediated antagonism improve right structure pulmonary artery banded pigs. Molecularly, restored cristae combatted downregulation proteins. Metabolomics lipidomics analyses revealed improved fatty acid Thus, these may be therapeutic target for RHF. Graphical

Language: Английский

Citations

1