Glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist tirzepatide promotes branched chain amino acid catabolism to prevent myocardial infarction in non-diabetic mice

Cardiovascular Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

A novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, tirzepatide (LY3298176, TZP), has been developed to treat Type 2 diabetes mellitus (T2DM). In ischaemic heart diseases, TZP is involved in cardiac metabolic processes. However, its efficacy safety treating failure (HF) following myocardial infarction (MI) remain uncertain. Herein, 12 week C57BL/6J mice were subjected MI surgery, followed by administration of TZP. The effects on function metabolism thoroughly assessed physiological, histological, cellular analyses. Downstream effectors screened through untargeted metabolomics analysis molecular docking. Construct a lower branched chain amino acid (BCAA) diet model determine whether TZP's cardioprotective effect associated with reducing BCAA levels. Our results demonstrated that reduced mortality MI, decreased the infarct area, attenuated cardiomyocyte necrosis. Pathological evaluation tissues increased fibrosis repair inflammatory infiltration. Mechanistically, uncovered positive correlation between catabolism pathway. docking verified could bind branched-chain keto dehydrogenase E1 subunit α (BCKDHA). BCKDHA phosphorylation at S293, enhanced catabolism, inhibited activation activating rapamycin (mTOR) signalling Furthermore, fed low-BCAA post-MI necrosis, repair, These further when used synergistically Taken together, our findings provide new perspectives unrecognized role protection. BCAA/mTOR pathway mice. Consequently, this study may present therapeutic options for patients HF.

Язык: Английский

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Myocardial Characterization on CT: Late Iodine Enhancement and Extracellular Volume

Echocardiography, Год журнала: 2025, Номер 42(2)

Опубликована: Фев. 1, 2025

ABSTRACT Myocardial tissue characterization is fundamental in diagnosing, treating, and managing various cardiac diseases. In recent years, computed tomography (CCT) emerged as a valuable alternative to magnetic resonance (CMR) for myocardial characterization, with the possibility detect scar quantify extracellular volume fraction single CT study advantage of combined coronary arteries evaluation, shorter scanning time, less susceptibility device artifacts compared CMR. However, CCT typically affected by lower contrast‐to‐noise ratio potentially increased radiation exposure. Therefore, deep understanding available technology strategies acquisition optimization importance improve image quality accuracy, while minimizing This review summarizes principles on CCT, protocols according different technologies including dual‐energy innovative photon‐counting detector CT, setting clinical utility.

Язык: Английский

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Necroptosis in myocardial ischaemia-reperfusion injury: current update on mechanisms, therapeutic targets, and translational potential

APOPTOSIS, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

Язык: Английский

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Ultrasmall PtIr Bimetallic Nanozyme Treats Myocardial Infarction via Ischemic/Inflammatory Cardiac Microenvironment Remodeling

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Myocardial infarction (MI) poses a serious threat to human health. MI induces oxidative damage and inflammation, leading myocardial death, scarring, ventricular remodeling. Nanozymes have shown potential alleviate reactive oxygen species (ROS)-induced treat cardiovascular diseases. In this study, we developed an ultrasmall PtIr bimetallic nanozyme MI. The exhibited robust superoxide dismutase- catalase-mimicking catalytic activities, modulating the conversion of excessive ROS into harmless products. Furthermore, treatment reduced levels apoptosis in cardiomyocyte AC16 cells under stress vitro, while increasing expression cardiomyocyte-related functional genes, including cTnT, cTnI, Cx43, ACTN2. It also maintained intracellular mitochondrial membrane potential, increased activity, protected structure. rat model, attenuated neutrophil extracellular trap formation, apoptosis, inflammation infarcted heart 1 week postadministration. Four weeks postadministration, significantly enhanced activity connectivity, infarct size fibrosis levels, microvascular density compared with phosphate-buffered saline or Ir treatment. Proteomic analysis revealed that proteins associated energy metabolism, function, contraction were upregulated, multiple pathways related function such as fatty acid β-oxidation citric cycle, enriched injection group. These results suggest remodels microenvironment by inflammatory response, repairing damaged myocardium, improving cardiac function. Our findings highlight promising therapeutic strategy for

Язык: Английский

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Rap2a promotes cardiac fibrosis and exacerbates myocardial infarction through the TNIK/Merlin/YAP axis

Cell Biology and Toxicology, Год журнала: 2025, Номер 41(1)

Опубликована: Май 7, 2025

Myocardial fibrosis constitutes the primary pathological characteristic of myocardial infarction (MI). The activation and proliferation fibroblasts serve as crucial factors in process development myocardium. Our research delved into role that Rap2a plays cardiac function well fibrosis, while its effects on cardial (CFs) proliferation, migration, phenotypic transformation were also explored. Examination GEO database showed a notable increase expression within tissue from mice with MI compared to normal mice. deficiency relieves restrains transition, migration CFs. absence mitigates Besides, it curbs growth CFs, restricts their movement, prevents them undergoing conversion. can bind TNIK enhance expression; Merlin/YAP signaling pathway was assessed downstream target further elucidate regulatory mechanism through which influences cardiomyocytes. In conclusion, this study provides evidence promotes mediating myofibroblast transformation, CFs via TNIK/Merlin/YAP pathway, thereby exacerbating symptoms infarction.

Язык: Английский

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How Advanced are Conductive Nanocomposite Hydrogels for Repairing and Monitoring Myocardial Infarction?

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 6777 - 6812

Опубликована: Май 1, 2025

Myocardial infarction (MI) remains the leading cause of death worldwide. Cardiomyocytes, being terminally differentiated cells, have limited regenerative capacity. Following an MI, myocyte necrosis and ventricular dilation can lead to heart failure. While current treatments for disease-such as pharmaceuticals, coronary interventions, artery bypass grafting, cellular therapy, transplantation-offer some relief, their effectiveness is limited, particularly in patients with severe myocardial damage. Recent advancements cardiac tissue engineering introduced a range materials aimed at repairing heart, conductive hydrogels emerging promising approach. These materials, which include metallic nanomaterials, polymers, carbon-based other specialized types substances, exhibit excellent electrical conductivity, tunable mechanical properties, biomimetic features. As result, they are increasingly considered repair. This review explores application treating infarction, highlighting recent research various hydrogels. categorized by nanomaterial composition, including designed cell culture scaffolds, patch-type hydrogels, injectable Additionally, electrophysiological monitoring during MI gaining importance understanding disease progression prognosis. In years, rapidly evolved serve tools real-time signal changes, while electroresponsive properties open new possibilities targeted drug delivery infarct therapy.

Язык: Английский

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Predictive Potential of CRTP5 and SII for Coronary Artery Severity and Myocardial Fibrosis in Patients with NSTE-ACS: An Exploratory Biomarker Study

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 7127 - 7138

Опубликована: Июнь 1, 2025

Язык: Английский

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Plasmapheresis as a Potential Generalizable Therapy for Myocardial Infarction

Rejuvenation Research, Год журнала: 2025, Номер unknown

Опубликована: Июнь 4, 2025

Myocardial infarction (MI) remains the leading cause of mortality and morbidity worldwide. It is caused by a thrombotic occlusion coronary vessel/s that leads to cardiomyocyte death. As response, inflammatory fibrotic responses are initiated replace necrotic tissue remodel heart. However, in most cases, these excessively activated, which accentuates injury causes adverse cardiac remodeling, often heart failure. This highly attributed dysregulated repair mechanism brought reduced regenerative capacity adult heart, chronic inflammation, other patient factors, such as comorbidities, diet, lifestyle. Because negative consequences excessive inflammation fibrosis post-MI responses, inhibiting factors associated with processes one major approaches MI management. Several therapies have been developed broadly and/or selectively inhibit inflammation- fibrosis-associated proteins over past decades shown promise addressing complications. challenges (e.g., off-targets, problems drug delivery, dosage, route, cost) efficacy interventions clinical setting remain. Hence, alternative optimally alleviate still much needed. In this review, we discuss possible use plasmapheresis, technique involves extracorporeal replacement blood plasma, treatment for MI. We provide an overview after focus on how plasmapheresis can be approach target pathways.

Язык: Английский

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To Repair a Broken Heart: Stem Cells in Ischemic Heart Disease

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(3), С. 2181 - 2208

Опубликована: Март 8, 2024

Despite improvements in contemporary medical and surgical therapies, cardiovascular disease (CVD) remains a significant cause of worldwide morbidity mortality; more specifically, ischemic heart (IHD) may affect individuals as young 20 years old. Typically managed with guideline-directed therapy, interventional or methods, the incurred cardiomyocyte loss is not always completely reversible; however, recent research into various stem cell (SC) populations has highlighted their potential for treatment perhaps regeneration injured cardiac tissue, either directly through cellular replacement indirectly local paracrine effects. Different types have been employed studies infarcted myocardium, both animal models myocardial infarction (MI) well clinical MI patients, including embryonic cells (ESCs) induced pluripotent (iPSCs), Muse cells, multipotent such bone marrow-derived mesenchymal (MSCs) progenitor (CSC/CPCs). These delivered is, form used to generate tissue-engineered (TE) constructs variable results. In this text, we sought perform narrative review experimental employing myocardium within last two decades, an emphasis on therapies administered thoracic incision percutaneous coronary interventions (PCI), elucidate possible mechanisms action therapeutic effects when manner.

Язык: Английский

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Comprehensive macro and micro views on immune cells in ischemic heart disease

Cell Proliferation, Год журнала: 2024, Номер 57(12)

Опубликована: Авг. 1, 2024

Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage failure. As complex pathologic condition, it involves intricate regulatory processes at cellular molecular levels. The immune system are closely interconnected, with cells playing crucial role maintaining cardiac health influencing progression. Consequently, alterations microenvironment influenced controlled by various cells, such as macrophages, neutrophils, dendritic eosinophils, T-lymphocytes, along cytokines they produce. Furthermore, studies have revealed Gata6

Язык: Английский

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