Network pharmacology-based prediction and molecular docking-based strategy to investigate the potential mechanism of Leonurus japonicus Houtt. Against myocardial ischemia reperfusion injury DOI Creative Commons
Xuan Liu,

Zilian Zhan,

Rui Zhang

et al.

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

Published: April 16, 2025

Leonurus japonicus Houtt. (LJH) has multiple pharmacological effects. To investigate the potential mechanism of LJH in treatment myocardial ischemia-reperfusion injury (MIRI) using network pharmacology, molecular docking technology, and vitro experiments. Herbs for ischemic heart disease were identified with help herb-disease databases. The TCMSP database was used to find targets LJH. Disease MIRI Disgenet, Genecard, Alliance Genome Resources common obtained VENN diagram, analyzed by GO function KEEG pathway enrichment predict action treating MIRI. With STRING Cytoscape software, we constructed a visual protein-protein interaction (PPI) model screen core then docked corresponding ligand molecules. AC16 cells simulate glucose-oxygen deprivation, apoptosis detected Annexin V-FITC/PI double staining; protein expression Western blot. one herbal remedies disease. had 247 26 These enriched TNF signaling NF-kappa B pathway, screened PPI results included TNF, VCAM1, MMP9. Molecular showed that compounds well target proteins. In experiments could inhibit elevation MMP9 after MIRI, reduce apoptosis, inflammation. mainly related activation regulation expression.

Language: Английский

The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery DOI Open Access
Jiaxin Deng, Qian Liu,

L Ye

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116337 - 116337

Published: Feb. 28, 2024

In myocardial ischemia/reperfusion injury (MIRI), moderate mitophagy is a protective or adaptive mechanism because of clearing defective mitochondria accumulates during MIRI. However, excessive lead to an increase in and ultimately exacerbate MIRI by causing overproduction uncontrolled production mitochondria. Phosphatase tensin homolog (PTEN)-induced kinase 1 (Pink1), Parkin, FUN14 domain containing (FUNDC1) B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B19KD interaction protein 3 (BNIP3) are the main mechanistic regulators Pink1 Parkin mitochondrial surface proteins involved ubiquitin-dependent pathway, while BNIP3 FUNDC1 receptor non-ubiquitin-dependent which play crucial role maintaining homeostasis quality. These can induce inhibit protect against but may also trigger insufficient mitophagy, thereby worsening condition. Understanding actions these provide valuable insights into pathological mechanisms underlying development. Based on above background, this article reviews through Pink1/Parkin pathway mediated led BNIP3, as well related drug treatment, aim effective strategies for prevention treatment

Language: Английский

Citations

37
Metrnl ameliorates myocardial ischemia–reperfusion injury by activating AMPK-mediated M2 macrophage polarization DOI Creative Commons
Dexin Chen,

Yang-Yi Feng,

Haiyan Wang

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: March 13, 2025

Abstract Background Meteorin-like hormone (Metrnl) is prominently expressed in activated M2 macrophages and has demonstrated potential therapeutic effects a range of cardiovascular diseases by modulating inflammatory responses. Nevertheless, its precise role the underlying mechanisms myocardial ischemia/reperfusion injury (MI/RI) are not fully understood. This study examined whether Metrnl can mitigate MI/RI through AMPK-mediated polarization macrophages. Methods In vivo, adeno-associated virus 9 containing F4/80 promoter (AAV9-F4/80) was utilized to overexpress mouse cardiac before surgery. vitro, bone marrow-derived (BMDMs) were treated with recombinant protein Metrnl, human cardiomyocyte cell line AC16 subjected hypoxia/reoxygenation (H/R) after co-culture supernatant these Cardiac function assessed via echocardiography, H&E staining, Evans blue-TTC staining. Inflammatory infiltration evaluated RT-qPCR ELISA, apoptosis Western blotting TUNEL macrophage immunofluorescence staining flow cytometry. Results overexpression significantly attenuated MI/RI, as evidenced reduced infarct size, enhancement function, diminished infiltration, decreased apoptosis. Furthermore, promoted M1 polarization. BMDMs shifted towards polarization, characterized expression cytokines (IL-1β, MCP-1, TNF-α) increased anti-inflammatory cytokine IL-10. Additionally, from Metrnl-treated protected cells under H/R conditions, BAX BCL-2 expression. However, inhibited AMPK inhibitor Compound C. Conclusions alleviates activating attenuate response highlights identifies it promising target for treatment ischemic heart disease.

Language: Английский

Citations

2
Iron chelators loaded on myocardiocyte mitochondria-targeted nanozyme system for treating myocardial ischemia-reperfusion injury in mouse models DOI Creative Commons
Ke Zhu, Kun Wang,

Rongting Zhang

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 15, 2025

Ferroptosis plays a critical role in myocardial ischemia-reperfusion injury (MIRI), posing significant clinical challenge. Nanoenzymes like cerium oxide (CeO2) hold promise for mitigating oxidative damage and inhibiting ferroptosis, but their delivery efficiency biological activity require optimization. This study aims to develop targeted nanozyme system MIRI treatment by integrating CeO2 with mesoporous polydopamine (mPDA) dexrazoxane (DXZ) achieve synergistic therapeutic effects. A biomineralization technique was used synthesize nanoparticles (2–3 nm) within mPDA, forming ~ 130 nm composite (Ce@mPDA). Surface modifications cardiac homing peptide (CHP) triphenylphosphine (TPP) enabled hierarchical targeting injured myocardium mitochondria. DXZ-loaded Ce@mPDA-C/P (D/Ce@mPDA-C/P) were evaluated vitro mouse model effects on stress, apoptosis, inflammation, function. D/Ce@mPDA-C/P exhibited robust ROS scavenging, sustained DXZ release, efficient mitochondrial targeting. The significantly reduced upregulated GPX4 expression, inhibited modulated the inflammatory microenvironment. Long-term studies demonstrated reductions fibrosis improvements function, including enhanced fractional shortening ejection fraction. effectively combines antioxidant properties of iron-chelating DXZ, providing promising strategy MIRI. approach may expand use advance nanomedicine-based interventions repair.

Language: Английский

Citations

1
Metrnl: a promising biomarker and therapeutic target for cardiovascular and metabolic diseases DOI Creative Commons
Wen‐Sheng Dong,

Can Hu,

Min Hu

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 5, 2024

Modern human society is burdened with the pandemic of cardiovascular and metabolic diseases. Metrnl a widely distributed secreted protein in body, involved regulating glucose lipid metabolism maintaining system homeostasis. In this review, we present predictive therapeutic roles various diseases, including atherosclerosis, ischemic heart disease, cardiac remodeling, failure, hypertension, chemotherapy-induced myocardial injury, diabetes mellitus, obesity.

Language: Английский

Citations

8
Cardiac endothelial ischemia/reperfusion injury-derived protein damage-associated molecular patterns disrupt the integrity of the endothelial barrier DOI Creative Commons
Sarawut Kumphune, Porrnthanate Seenak,

Nitchawat Paiyabhrom

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(2), P. e24600 - e24600

Published: Jan. 1, 2024

Human cardiac microvascular endothelial cells (HCMECs) are sensitive to ischemia and vulnerable damage during reperfusion. The release of damage-associated molecular patterns (DAMPs) reperfusion induces additional tissue damage. current study aimed identify early protein DAMPs in human subjected ischemia-reperfusion injury (IRI) using a proteomic approach their effect on cell injury. HCMECs were 60 min simulated 6 h reperfusion, which can cause lethal the culture media liquid chromatography-tandem mass spectrometry analysis. treated with IRI-derived DAMP medium for 24 h. Endothelial was assessed by measuring lactate dehydrogenase activity, morphological features, expression cadherin, nitric oxide synthase (eNOS), caveolin-1. top two upregulated proteins, DNAJ homolog subfamily B member 11 pyrroline-5-carboxylate reductase 2, promising predictors expose DAMP, activity significantly increased compared control group (10.15 ± 1.03 vs 17.67 1.19, respectively). Following treatment DAMPs, actin-filament dysregulation, downregulation vascular caveolin-1, eNOS expressions observed, along death. In conclusion, released IRI could serve as novel candidate biomarkers acute myocardial IRI. Distinct features impaired plasma membrane integrity help therapeutic targets mitigate detrimental consequences mediated DAMPs.

Language: Английский

Citations

6
Exosomes-Mediated Signaling Pathway: A New Direction for Treatment of Organ Ischemia-Reperfusion Injury DOI Creative Commons
Yanying Wang, Ruojiao Xu,

Yujia Yan

et al.

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

Citations

6
Mitochondrial Stress as a Central Player in the Pathogenesis of Hypoxia-Related Myocardial Dysfunction: New Insights DOI Creative Commons

Zhijiang Guo,

Yingjie Tian, Nanyang Liu

et al.

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(13), P. 2502 - 2509

Published: Jan. 1, 2024

Hypoxic injury is a critical pathological factor in the development of various cardiovascular diseases, such as congenital heart disease, myocardial infarction, and failure. Mitochondrial quality control essential for protecting cardiomyocytes from hypoxic damage. Under conditions, disruptions mitochondrial homeostasis result excessive reactive oxygen species (ROS) production, imbalances dynamics, initiate processes including oxidative stress, inflammatory responses, apoptosis. Targeted interventions to enhance control, coenzyme Q10 statins, have shown promise mitigating hypoxia-induced dysfunction. These treatments offer potential therapeutic strategies hypoxia-related diseases by regulating fission fusion, restoring biogenesis, reducing ROS promoting mitophagy.

Language: Английский

Citations

6
Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications DOI
Xing Chen, Yang Yang, Zheng Zhou

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 112930 - 112930

Published: Aug. 14, 2024

Language: Английский

Citations

5
Adipokines and their potential impacts on susceptibility to myocardial ischemia/reperfusion injury in diabetes DOI Creative Commons

Ronghui Han,

Hemeng Huang,

Jianyu Zhu

et al.

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 13, 2024

Abstract Coronary artery disease has a high mortality rate and is striking public health concern, affecting substantial portion of the global population. On early onset myocardial ischemia, thrombolytic therapy coronary revascularization could promptly restore bloodstream nutrient supply to ischemic tissue, efficiently preserving less severely injured myocardium. However, abrupt re-establishment blood flow triggers significant discharge previously accumulated oxidative substances inflammatory cytokines, leading further harm referred as ischemia/reperfusion (I/R) injury. Diabetes significantly raises vulnerability heart I/R injury due disrupted glucose lipid processing, impaired insulin sensitivity metabolic signaling, increased responses. Numerous studies have indicated that adipokines are crucial in etiology pathogenesis obesity, diabetes, hyperlipidemia, hypertension, disease. Adipokines such adiponectin, adipsin, visfatin, chemerin, omentin, apelin, which possess protective properties against activity resistance, been shown confer protection conditions atherosclerosis, hypertrophy, injury, diabetic complications. other hand, leptin resistin, known for their pro-inflammatory characteristics, linked elevated cardiac deposition, fibrosis. Meteorin-like (metrnl) exhibits opposite effects various pathological conditions. data on I/R, especially still incomplete controversial. This review focuses recent research regarding categorization function muscle, identification different signaling pathways involved under conditions, aiming facilitate exploration therapeutic strategies diabetes.

Language: Английский

Citations

4
Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway DOI Open Access

Aizhen Zhao,

Wangrui Lei,

Jiayin Tian

et al.

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

Citations

0