Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(11), P. 4458 - 4475

Published: Jan. 1, 2024

This study investigated the mechanism by which NR4A1 regulates mitochondrial fission factor (Mff)-related and FUN14 domain 1 (FUNDC1)-mediated mitophagy following cardiac ischemia-reperfusion injury(I/R). Our findings showed that damage regulation was positively correlated with pathological pan-apoptosis of myocardial cell mitochondria. Compared wild-type mice (WT), NR4A1-knockout exhibited resistance to injury fission, characterized activation. Results increased expression level, activating mediated Mff restoring phenotype FUNDC1. The inactivation FUNDC1 phosphorylation could not mediate normalization in a timely manner, leading an excessive stress response unfolded proteins imbalance homeostasis. process disrupted quality control network, accumulation damaged mitochondria activation pan-apoptotic programs. data indicate is novel critical target I/R exertsand negative regulatory effects Mff-mediated mito-fission inhibiting FUNDC1-mediated mitophagy. Targeting crosstalk balance between NR4A1-Mff-FUNDC1 potential approach for treating I/R.

Language: Английский

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Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 256 - 256

Published: Feb. 23, 2025

Endothelial dysfunction (ED) is characterized by an imbalance between vasodilatory and vasoconstrictive factors, leading to impaired vascular tone, thrombosis, inflammation. These processes are critical in the development of cardiovascular diseases (CVDs) such as atherosclerosis, hypertension ischemia/reperfusion injury (IRI). Reduced nitric oxide (NO) production increased oxidative stress key contributors ED. Aging further exacerbates ED through mitochondrial oxidative/nitrosative stress, heightening CVD risk. Antioxidant systems like superoxide-dismutase (SOD), glutathione-peroxidase (GPx), thioredoxin/thioredoxin-reductase (Trx/TXNRD) pathways protect against stress. However, their reduced activity promotes ED, vulnerability IRI. Metabolic syndrome, comprising insulin resistance, obesity, hypertension, often accompanied Specifically, hyperglycemia worsens endothelial damage promoting Obesity leads chronic inflammation changes perivascular adipose tissue, while associated with increase The NLRP3 inflammasome plays a significant role being triggered factors reactive oxygen nitrogen species, ischemia, high glucose, which contribute inflammation, injury, exacerbation Treatments, N-acetyl-L-cysteine, SGLT2 or inhibitors, show promise improving function. Yet complexity suggests that multi-targeted therapies addressing metabolic disturbances essential for managing CVDs syndrome.

Language: Английский

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Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target

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

Published: Oct. 1, 2024

Language: Английский

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Assessing platelet-derived extracellular vesicles for potential as therapeutic targets in cardiovascular diseases

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: Jan. 16, 2025

Introduction Cardiovascular disease (CVD) is the leading cause of death worldwide. Platelet-derived extracellular vesicles (PEV) have attracted extensive attention in cardiovascular research recent years because their cargo involved a variety pathophysiological processes, such as thrombosis, immune response, promotion or inhibition inflammatory angiogenesis well cell proliferation and migration.

Language: Английский

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Ischemic Area‐Targeting and Self‐Monitoring Nanoprobes Ameliorate Myocardial Ischemia/Reperfusion Injury by Scavenging ROS and Counteracting Cardiac Inflammation

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real‐time monitoring drug aggregation the MIRI region remains an open question. Herein, delivery system, hesperadin ICG assembled PLGA‐Se‐Se‐PEG‐IMTP (HI@PSeP‐IMTP), designed to deliver for vivo optical imaging tracking ameliorate MIRI. The peak nanoprobes monitored by near‐infrared fluorescence photoacoustic imaging. maximal signals HI@PSeP‐IMTP group rise ≈32% 40% respectively compared with that HI@PSeP group. Moreover, effectively mitigates due synergistic integration diselenide bonds hesperadin, which can eliminate ROS suppress cardiac inflammation. Specifically, expression levels p‐CaMKII, p‐IκBα, p65 demonstrate reduction 30%, 46%, 42% PBS Collectively, provides new insights into development drugs integrating diagnosis treatment

Language: Английский

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Lipid Nanoparticle-Mediated Oip5-as1 Delivery Preserves Mitochondrial Function in Myocardial Ischemia/Reperfusion Injury by Inhibiting the p53 Pathway

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(45), P. 61565 - 61582

Published: Nov. 1, 2024

Myocardial ischemia/reperfusion (MI/R) injury, a major contributor to poor prognosis in patients with acute myocardial infarction, currently lacks effective therapeutic strategies clinical practice. The long noncoding RNA (lncRNA) Oip5-as1 can regulate various cellular processes, such as cell proliferation, differentiation, and survival. may have potential target for MI/R injury its upregulated expression has been associated reduced infarct size improved cardiac function animal models, although how effectively safely overexpress vivo remains unclear. Lipid nanoparticles (LNPs) are versatile technology targeted drug delivery numerous applications. Herein, we aimed assess the efficacy safety of LNPs coloaded cardiomyocyte-specific binding peptide (LNP@Oip5-as1@CMP) murine model injury. To achieve this, LNP@Oip5-as1@CMP was synthesized via ethanol injection method. structural components were physicochemically analyzed. A hypoxia/reoxygenation (H/R) HL-1 cells coronary artery ligation mice used simulate Our results demonstrated that designed cardiomyocyte targeting efficient successfully synthesized. In cells, treatment significantly mitochondrial apoptosis caused by H/R model, intravenous administration decreased function. Mechanistic investigations revealed inhibited p53 signaling pathway. However, cardioprotective effects abrogated administrating Nutlin-3a, activator. Furthermore, no signs organ damage detected after injection. study reveals mitigating These findings pave way advanced treatments cardiovascular diseases, emphasizing promise lncRNA-based therapies.

Language: Английский

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Identification and validation of mitochondrial dynamics-related genes in patients with acute myocardial infarction-a bioinformatics analysis

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Recent studies highlight the link between cardiovascular disease and mitochondrial dynamics. This study sought biomarkers of dynamics in acute myocardial infarction (AMI) to guide more precise clinical management. AMI-related datasets (GSE62646 GSE59867) 50 dynamics-related genes (MD-RGs) were derived from public databases. Firstly, based on MD-RGs, AMI samples GSE62646 classified into high- low-scoring groups by single-sample gene set enrichment analysis. The differentially expressed (DEGs) incorporated machine learning algorithms. Subsequent expression level receiver operating characteristic (ROC) analyses identified biomarkers. Furthermore, relationship was analyzed analysis, immune infiltration correlation analysis m6A regulators. Finally, biomarker verified reverse transcription quantitative PCR (RT-qPCR). In this study, COX7B SNORD54 as associated with AMI. ROC curves showed that two could better differentiate control samples, subsequent nomogram created integrating highly accurate predicting revealed co-enrich pathways for included “oxidative phosphorylation” “Notch signaling pathway”. Notably, six regulators (HNRNPC, KIAA1429, METTL3, WTAP, YTHDC1, YTHDC2) found be significantly under-expressed samples. RT-PCR demonstrated levels downregulated compared controls. recognized AMI, presenting potential applications advance understanding

Language: Английский

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Impact of controlled stepwise reperfusion during primary percutaneous coronary intervention on patients with ST-elevation myocardial infarction

Clinical Hemorheology and Microcirculation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Objective: The aim of this study is to examine the impact controlled stepwise reperfusion by modulating pre-dilation balloon pressure during primary percutaneous coronary interventions (PPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Consecutive STEMI requiring PPCI thrombolysis (TIMI) flow grades 0 or 1, were randomly divided into an experimental group and a control group. For group, was removed immediately after achieving antegrade perfusion beyond lesion. underwent reperfusion, being gradually reduced. Baseline data, intra/post-procedural 3-month left ventricular ejection fraction (LVEF), major adverse cardiac events (MACE) documented compared between two groups. Results: experienced more severe symptoms procedure ( p = 0.034), higher post-procedural corrected TIMI frame counts 0.047), significant hemodynamic changes 0.031), increased rates tachycardia/ventricular fibrillation 0.035). Additionally, they had total number arrhythmias 0.017), lower 90-min ST segment resolution rate 0.045), elevated cTNI levels one week 0.047). Three months later, demonstrated LVEF 0.048) trend towards drug-treated 0.073). No differences observed other statistical results. Conclusion: In undergoing PPCI, adjusting effectively reduces ischemia-reperfusion injury, improves perfusion, supports recovery function.

Language: Английский

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Cardioprotective potential of transcription factor PRRX1 silencing against myocardial ischemia/reperfusion injury by regulating excessive mitophagy and ferroptosis through FKBP5-p38 MAPK axis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167766 - 167766

Published: March 3, 2025

Language: Английский

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Association of Intramyocardial Hemorrhage With Inflammatory Biomarkers in Patients With ST-Segment Elevation Myocardial Infarction

JACC Advances, Journal Year: 2025, Volume and Issue: 4(4), P. 101647 - 101647

Published: March 12, 2025

Language: Английский

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