The Janus face of mitophagy in myocardial ischemia/reperfusion injury and recovery

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 173, С. 116337 - 116337

Опубликована: Фев. 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

Язык: Английский

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Iron chelators loaded on myocardiocyte mitochondria-targeted nanozyme system for treating myocardial ischemia-reperfusion injury in mouse models

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 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.

Язык: Английский

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

Biomedicines, Год журнала: 2024, Номер 12(2), С. 353 - 353

Опубликована: Фев. 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

Язык: Английский

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Metrnl: a promising biomarker and therapeutic target for cardiovascular and metabolic diseases

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Авг. 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.

Язык: Английский

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Cardiac endothelial ischemia/reperfusion injury-derived protein damage-associated molecular patterns disrupt the integrity of the endothelial barrier

Heliyon, Год журнала: 2024, Номер 10(2), С. e24600 - e24600

Опубликована: Янв. 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.

Язык: Английский

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

International Journal of Medical Sciences, Год журнала: 2024, Номер 21(13), С. 2502 - 2509

Опубликована: Янв. 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.

Язык: Английский

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

Phytotherapy Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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

Язык: Английский

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The Proteomic Landscape of the Coronary Accessible Heart Cell Surfaceome

PROTEOMICS, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

ABSTRACT Cell surface proteins (surfaceome) represent key signalling and interaction molecules for therapeutic targeting, biomarker profiling cellular phenotyping in physiological pathological states. Here, we employed coronary artery perfusion with membrane‐impermeant biotin to label capture the surface‐accessible proteome neo‐native (intact) heart. Using quantitative proteomics, identified 701 heart cell surfaceome accessible by artery, including receptors, enzymes, adhesion junctional molecules. This comprises 216 cardiac cell‐specific proteins, 29 reported cardiomyocytes (CXADR, CACNA1C), 12 fibroblasts (ITGA8, COL3A1) 63 multiple types (ICAM1, SLC3A2, CDH2). Further, this 53 enriched tissue compared other tissues humans implicated networks involving cardiomyopathy (CDH2, DTNA, PTKP2, SNTA1, CAM, K2D/B), muscle contraction development (ENG, SGCG, MYPN), calcium ion binding (SGCA, MASP1, THBS4, FBLN2, GSN) metabolism (SDHA, NUDFS1, GYS1, ACO2, IDH2). method offers a powerful tool dissecting molecular landscape of surfaceome, its role maintaining vascular function, potential leads studying interactions systemic delivery

Язык: Английский

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Geriatric nutritional risk index as a predictor of 30-day and 365-day mortality in patients with acute myocardial infarction: a retrospective cohort study using the MIMIC-IV database

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Фев. 5, 2025

Background The Geriatric Nutritional Risk Index (GNRI) is a clinical indicator for evaluating the nutritional status of patients, but its role in short-term prognosis patients with acute myocardial infarction still not fully understood. This study aims to explore correlation between GNRI and overall mortality within 30 days 365 those (AMI). Methods A retrospective analysis was performed utilizing Medical Information Mart Intensive Care IV (MIMIC-IV) database. included 895 diagnosed AMI identified through ICD9 ICD10 codes (410, I21, I23) who were hospitalized first time due AMI. Subjects classified into four groups according GNRI: high (GNRI <82, n = 110), moderate (82 ≤ <92, 205), low (92 <98, 225), no risk ≥98, 355). Restricted cubic splines (RCS) threshold effect analyses applied non-linear relationship mortality. Subgroup conducted based on gender, hypertension, diabetes, stroke, hyperlipidemia, chronic obstructive pulmonary disease, age. mediation investigate impact lymphocytes association Results In an sample elevated correlated reduced 30-day (HR 0.937, 95% CI: 0.917–0.957, p < 0.001) 365-day 0.923–0.950, 0.001). trend categories indicated significant decline associated rising (P <0.001). validated consistency such results throughout diverse patient characteristics. significantly mediated (ACME: 0.022, 0.003–0.180, landmark at 20 after admission further demonstrated during different phases recovery. Conclusion highlights prognostic value predicting long-term emphasizing significance inflammatory indicators therapy assessment these individuals.

Язык: Английский

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Unraveling the complex interplay between Mitochondria-Associated Membranes (MAMs) and cardiovascular Inflammation: Molecular mechanisms and therapeutic implications

International Immunopharmacology, Год журнала: 2024, Номер 141, С. 112930 - 112930

Опубликована: Авг. 14, 2024

Язык: Английский

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