Inflammation in Myocardial Ischemia/Reperfusion Injury: Underlying Mechanisms and Therapeutic Potential

Antioxidants, Journal Year: 2023, Volume and Issue: 12(11), P. 1944 - 1944

Published: Oct. 31, 2023

Acute myocardial infarction (MI) occurs when blood flow to the myocardium is restricted, leading cardiac damage and massive loss of viable cardiomyocytes. Timely restoration coronary considered gold standard treatment for MI patients limits infarct size; however, this intervention, known as reperfusion, initiates a complex pathological process that somewhat paradoxically also contributes injury. Despite being sterile environment, ischemia/reperfusion (I/R) injury triggers inflammation, which expansion subsequent remodeling wound healing. The immune response comprised subsets both myeloid lymphoid-derived cells act in concert modulate pathogenesis resolution I/R Multiple mechanisms, including altered metabolic status, regulate cell activation function setting acute MI, yet our understanding remains incomplete. While numerous studies demonstrated benefit following strategies target inflammation preclinical models, therapeutic attempts mitigate were less successful. Therefore, further investigation leveraging emerging technologies needed better characterize intricate inflammatory elucidate its influence on progression heart failure.

Language: Английский

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Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia–Reperfusion Injury through NR4A2-Mediated Mitophagy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3305 - 3305

Published: March 14, 2024

Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells the endothelium have recently been reported promote cardiomyocyte through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, mechanism SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at time this writing. The present study utilized mice model ischemia/reperfusion (I/R) demonstrate that administration via tail vein injection significantly diminished severity I/R-induced cardiac damage and prevented apoptosis cardiomyocytes. Moreover, was here identified as primary mediator observed protective effects VEC-Exos. In addition, within investigation, in vitro experiments using cardiomyocytes showed counteracted I/R injury activating Parkin nuclear receptor subfamily group A member 2/optineurin (NR4A2/OPTN) pathways, turn resulting increased levels mitophagy I/R-affected myocardium. highlights potential therapeutic SPC-rich secreted VECs on alleviating cardiomyocytes, thereby providing strong experimental evidence support application target prevention treatment infarction.

Language: Английский

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Ginsenoside Rd: A promising target for ischemia-reperfusion injury therapy (A mini review)

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116111 - 116111

Published: Jan. 5, 2024

Ischemia-reperfusion injury (IRI) represents a prevalent pathological phenomenon. Traditional treatment approaches primarily aim at restoring blood supply to ischemic organs, disregarding the consequent damage caused by IRI. Belonging class of protopanaxadiol ginsenosides that are found in Panax ginseng, ginsenoside Rd (GSRd) demonstrates notable safety alongside diverse range biological functions. Its active components exhibit pharmacological effects, encompassing anti-inflammatory, anti-tumor, neuroprotective, cardiovascular-protective, and immune-regulatory properties, making it promising candidate for addressing multiple medical conditions. GSRd shields against I/R employing crucial cellular mechanisms, including attenuation oxidative stress, reduction inflammation, promotion cell survival signaling pathways, inhibition apoptotic pathways. Additionally, regulates mitochondrial function, maintains calcium homeostasis, modulates expression genes involved injury. This review seeks consolidate mechanism action within context Our objective is contribute advancement GSRd-related pharmaceuticals provide novel insights clinicians developing IRI strategies.

Language: Английский

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Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 353 - 353

Published: Feb. 2, 2024

Ischemia reperfusion (I/R) is a common pathological process which occurs mostly in organs like the heart, brain, kidney, and lung. The injury caused by I/R gradually becomes one of main causes fatal diseases, an urgent clinical problem to be solved. Although great progress has been made therapeutic methods, including surgical, drug, gene therapy, transplant therapy for injury, development effective methods cure remains worldwide challenge. In recent years, exosomes have attracted much attention their important roles immune response, antigen presentation, cell migration, differentiation, tumor invasion. Meanwhile, shown potential treatment organs. study exosome-mediated signaling pathway can not only help reveal mechanism behind promoting recovery, but also provide theoretical basis application exosomes. Here, we review research utilizing various from different types promote healing focusing on classical pathways such as PI3K/Akt, NF-κB, Nrf2, PTEN, Wnt, MAPK, toll-like receptor, AMPK. results suggest that regulate these reduce oxidative stress, responses, decrease expression inflammatory cytokines, tissue repair, making competitive emerging vector treating damage

Language: Английский

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METTL3 boosts mitochondrial fission and induces cardiac fibrosis after ischemia/reperfusion injury

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 20(2), P. 433 - 445

Published: Dec. 5, 2023

METTL3, an RNA methyltransferase enzyme, exerts therapeutic effects on various cardiovascular diseases.Myocardial ischemia-reperfusion injury (MIRI) and subsequently cardiac fibrosis is linked to acute cardiomyocyte death or dysfunction induced by mitochondrial damage, particularly fission.Our research aims elucidate the potential mechanisms underlying actions of METTL3 in MIRI, with focus fission.When compared Mettl3 flox mice subjected knockout (Mettl3 Cko ) have reduced infarct size, decreased serum levels myocardial injury-related factors, limited fibrosis, preserved ultrastructure contractile/relaxation capacity.The cardioprotective were associated inflammatory responses, neutrophil infiltration, suppression death.Through signaling pathway validation experiments assays cultured HL-1 cardiomyocytes exposed hypoxia/reoxygenation, we confirmed that deficiency interfere DNA-PKcs phosphorylation, thereby blocking downstream activation Fis1 preventing pathological fission.In conclusion, this study confirms inhibition can alleviate inflammation prevent under reperfusion conditions disrupting DNA-PKcs/Fis1-dependent fission, ultimately improving function.These findings suggest new approaches for clinical intervention patients MIRI.

Language: Английский

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PEDF and 34‐mer peptide inhibit cardiac microvascular endothelial cell ferroptosis via Nrf2/HO‐1 signalling in myocardial ischemia‐reperfusion injury

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(14)

Published: July 1, 2024

Myocardial ischemia-reperfusion injury (MIRI) represents a critical pathology in acute myocardial infarction (AMI), which is characterized by high mortality and morbidity. Cardiac microvascular dysfunction contributes to MIRI, potentially culminating heart failure (HF). Pigment epithelium-derived factor (PEDF), belongs the non-inhibitory serpin family, exhibits several physiological effects, including anti-angiogenesis, anti-inflammatory antioxidant properties. Our study aims explore impact of PEDF its functional peptide 34-mer on both cardiac perfusion MIRI rats human endothelial cells (HCMECs) under hypoxia reoxygenation (HR). It has been shown that accompanied ferroptosis HCMECs. Furthermore, we investigated effect 34-mer, particularly regarding Nrf2/HO-1 signalling pathway. results demonstrated significantly ameliorated following MIRI. Additionally, they exhibited notable suppression HCMECs, these effects were mediated through activation signalling. These findings highlight therapeutic potential alleviating By enhancing mitigating ferroptosis, derivative represent promising candidates for treatment AMI.

Language: Английский

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Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

ABSTRACT Ischemia reperfusion‐induced myocardial injury is a prominent pathological feature in patients with coronary artery disease, contributing to significant mortality and morbidity rates. Mangiferin (MGF), the main active ingredient extracted from Anemarrhena asphodeloides Bge , has anti‐inflammatory, anti‐oxidation, anti‐diabetes, anti‐tumor effects. The present study confirmed that GAS6/Axl pathway was identified as promising novel target for treatment of ischemia reperfusion (IR) injury. However, whether MGF exerts anti‐myocardial through still unclear. In this study, BALB/c male mice HL‐1 cardiomyocytes were used construct model IR hypoxia‐reoxygenation (HR) (or H 2 O ) vivo vitro, respectively. significantly improved cardiac function indicators, structure, enzymes, mitochondrial function, together reduced oxidative stress apoptosis IR‐injured mice. increased cell viability, inhibited release LDH, apoptosis, both HR ‐injured cells. particular, signaling plays an important role process. Additionally, we also demonstrated GAS6 gene knockout reversed protective effect against cardiomyocytes. effects by activating pathway, providing theoretical basis potential cardioprotective drug clinical setting

Language: Английский

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Mechanisms of mitochondrial damage-associated molecular patterns associated with inflammatory response in cardiovascular diseases

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 13, 2025

Language: Английский

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miRNA-541-5p regulates myocardial ischemia–reperfusion injury by targeting ferroptosis

Journal of Cardiothoracic Surgery, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 15, 2025

This article aims to use high-throughput sequencing identify miRNAs associated with ferroptosis in myocardial ischemia–reperfusion injury, select a target miRNA, and investigate its role H9C2 cells hypoxia-reoxygenation injury. SD rats were used as subjects. ELISA kits quantified MDA, SOD, GSH, LDH, ferritin levels. TTC staining evaluated infarction size. HE observed histopathological changes. DCFH-DA fluorescent probe detected ROS. CCK-8 kit measured cell viability. HiSeq 2000 performed differential expression analysis of miRNAs. qRT-PCR Western blots assessed the levels GPX-4, ACSL-4, HO-1, TFR-1 TFR-2. SPSS 21.0 software conducted statistical analysis. Myocardial injury resulted decreased SOD increased LDH up-regulation ferritin, TFR-2, down-regulation tissue damage, accumulation However, DFO treatment reversed these Subsequently, gene miRNA-541-5p was obtained by miRNA screening, further validation revealed that tissues I/R model group compared those NC group, P < 0.05. constructing lines overexpression inhibition, inversely correlated survival after led decrease an increase wb qRT-PCT demonstrated high up-regulated protein/mRNA TFR-1, but down-regulated GPX-4. In addition, ADAM 7, FNIP 2, HOXD 10, HCCS STK 3 preliminarily identified potential candidate genes for bioinformatics Among them, ADAM7 emerges most suitable based on selection criteria. summary, may be biomarker damage diseases can regulate oxidative stress iron death inhibiting miRNA-541-5p, thereby reducing mechanisms

Language: Английский

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CircHIPK2 recruits SRSF1 to increase TXNIP mRNA stability and promotes autophagy-dependent ferroptosis and apoptosis in myocardial ischemia-reperfusion injury

Journal of Cardiothoracic Surgery, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 4, 2025

Myocardial ischemia/reperfusion injury (MIRI) secondary to acute myocardial infarction (AMI) can lead cardiomyocyte death and impaired cardiac function. Studies have confirmed that circular RNAs (circRNAs) play an important role in MIRI. In this study, the mechanism of circHIPK2 MIRI were evaluated. Human myocytes (HCM) cultured under Hypoxia/Reoxygenation (H/R) condition establish a model vitro. Expression circHIPK2, SRSF1 TXNIP was assessed using RT-qPCR. Protein levels autophagy markers (LC3II/LC3I, Beclin1, p62) ferroptosis (GPX4, FTH1, ACSL4) detected by Western blot. Cell viability apoptosis CCK-8 flow cytometry. Levels oxidative stress (MDA, SOD) inflammatory factors (IL-6, IL-1β, TNF-α) tested ELISA assay. Iron concentration measured with iron detection kit. Location cells RNA-nucleosome separation RIP ChIP assays verified relationship between TXNIP. mRNA stability dertermined actinomycin D. Infarct area examined TTC staining (I/R) mouse model. HE evaluated injury. CircHIPK2 increased H/R-induced HCM cells. downregulation suppressed stress, autophagy-dependent induced H/R. Additionally recruited target stabilized expression. We further demonstrated upregulation overturned therapeutic effects silencing on H/R vivo, improved dysfunction caused I/R. Our results demonstrate contributes through inducing via SRSF1/TXNIP axis, offering new insights into treatment.

Language: Английский

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