Transfer learning enables predictions in network biology

Nature, Год журнала: 2023, Номер 618(7965), С. 616 - 624

Опубликована: Май 31, 2023

Язык: Английский

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Mitochondrial dysfunction in human hypertrophic cardiomyopathy is linked to cardiomyocyte architecture disruption and corrected by improving NADH-driven mitochondrial respiration

European Heart Journal, Год журнала: 2023, Номер 44(13), С. 1170 - 1185

Опубликована: Янв. 12, 2023

Abstract Aims Genetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs the absence a mutation genotype-negative Mitochondrial dysfunction thought to be key driver pathological remodelling HCM. Reports mitochondrial respiratory function and specific disease-modifying treatment options patients with are scarce. Methods results Respirometry was performed on septal myectomy tissue from (n = 59) evaluate oxidative phosphorylation fatty acid oxidation. most notably reflected impaired NADH-linked respiration. but not respiration markedly depressed indexed thickness ≥10 compared <10. explained reduced abundance or fragmentation mitochondria, as evaluated transmission electron microscopy. Rather, improper organization mitochondria relative myofibrils (expressed percentage disorganized mitochondria) strongly associated dysfunction. Pre-incubation cardiolipin-stabilizing drug elamipretide raising NAD+ levels both boosted Conclusion cardiomyocyte architecture disruption linked hypertrophy Despite severe myocardial were responsive treatments aimed at restoring function, eliciting target prevent ameliorate cardiac disease Mitochondria-targeting therapy may particularly benefit HCM, given tight link between impairment thickening this subpopulation.

Язык: Английский

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Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease

Cells, Год журнала: 2024, Номер 13(4), С. 353 - 353

Опубликована: Фев. 17, 2024

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are primary cause death worldwide, with an immense impact on patient quality life and disability. According to World Health Organization, CVD takes estimated 17.9 million lives each year, where more than four out five deaths due attacks strokes. In decades come, increased prevalence age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular disease, failure (HF) will contribute even greater health economic burden global average expectancy increases consequently world’s population continues age. Considering this, it is important focus our research efforts understanding fundamental mechanisms underlying CVD. this review, we cellular senescence mitochondrial dysfunction, which have long been established We also assess recent advances in targeting dysfunction including energy starvation oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, therapies that influence both therefore perhaps represent strategies most clinical potential, range, utility.

Язык: Английский

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Vitamin C as Scavenger of Reactive Oxygen Species during Healing after Myocardial Infarction

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3114 - 3114

Опубликована: Март 7, 2024

Currently, coronary artery bypass and reperfusion therapies are considered the gold standard in long-term treatments to restore heart function after acute myocardial infarction. As a drawback of these restoring strategies, an ischemic insult sudden oxygen exposure lead exacerbated synthesis additional reactive oxidative species persistence increased oxidation levels. Attempts based on antioxidant treatment have failed achieve effective therapy for cardiovascular disease patients. The controversial use vitamin C as clinical practice is comprehensively systematized discussed this review. dose-dependent adsorption release kinetics mechanism complex; however, review may provide holistic perspective its potential preventive supplement and/or combined precise targeted therapeutics management therapy.

Язык: Английский

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Mitochondrial dysfunction in AMI: mechanisms and therapeutic perspectives

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

Опубликована: Апрель 10, 2025

Acute myocardial infarction (AMI) and the ischemia-reperfusion injury (MI/RI) that typically ensues represent a significant global health burden, accounting for considerable number of deaths disabilities. In context AMI, percutaneous coronary intervention (PCI) is preferred treatment option reducing acute ischemic damage to heart. Despite modernity PCI therapy, pathological cardiomyocytes due MI/RI remains an important target affects long-term prognosis patients. recent years, mitochondrial dysfunction during AMI has been increasingly recognized as critical factor in cardiomyocyte death. Damaged mitochondria play active role formation inflammatory environment by triggering key signaling pathways, including those mediated cyclic GMP-AMP synthase, NOD-like receptors Toll-like receptors. This review emphasizes dual both contributors regulators inflammation. The aim explore complex mechanisms its profound impact on immune dysregulation. Specific interventions mitochondrial-targeted antioxidants, membrane-stabilizing peptides, transplantation therapies have demonstrated efficacy preclinical models.

Язык: Английский

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Mitochondrial Ca2+ Signaling in Health, Disease and Therapy

Cells, Год журнала: 2021, Номер 10(6), С. 1317 - 1317

Опубликована: Май 25, 2021

The divalent cation calcium (Ca2+) is considered one of the main second messengers inside cells and acts as most prominent signal in a plethora biological processes. Its homeostasis guaranteed by an intricate complex system channels, pumps, exchangers. In this context, regulating cellular Ca2+ levels, mitochondria control both uptake release Ca2+. Therefore, at mitochondrial level, plays dual role, participating vital physiological processes (ATP production regulation metabolism) pathophysiological (cell death, cancer progression metastasis). Hence, it not surprising that alterations (mCa2+) pathways or mutations transporters affect activities functions entire cell. Indeed, widely recognized dysregulation mCa2+ signaling leads to various pathological scenarios, including cancer, neurological defects cardiovascular diseases (CVDs). This review summarizes current knowledge on homeostasis, related mechanisms significance physiology human diseases. We also highlight strategies aimed remedying promising therapeutical approaches.

Язык: Английский

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Calcium dysregulation in heart diseases: Targeting calcium channels to achieve a correct calcium homeostasis

Pharmacological Research, Год журнала: 2022, Номер 177, С. 106119 - 106119

Опубликована: Фев. 5, 2022

Язык: Английский

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Mitochondrial quality control in health and cardiovascular diseases

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Ноя. 6, 2023

Cardiovascular diseases (CVDs) are one of the primary causes mortality worldwide. An optimal mitochondrial function is central to supplying tissues with high energy demand, such as cardiovascular system. In addition producing ATP a power source, mitochondria also heavily involved in adaptation environmental stress and fine-tuning tissue functions. Mitochondrial quality control (MQC) through fission, fusion, mitophagy, biogenesis ensures clearance dysfunctional preserves homeostasis tissues. Furthermore, generate reactive oxygen species (ROS), which trigger production pro-inflammatory cytokines regulate cell survival. dysfunction has been implicated multiple CVDs, including ischemia-reperfusion (I/R), atherosclerosis, heart failure, cardiac hypertrophy, hypertension, diabetic genetic cardiomyopathies, Kawasaki Disease (KD). Thus, MQC pivotal promoting health. Here, we outline mechanisms discuss current literature on CVDs.

Язык: Английский

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LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2

Circulation Research, Год журнала: 2024, Номер 134(4), С. 425 - 441

Опубликована: Фев. 1, 2024

Human cardiac long noncoding RNA (lncRNA) profiles in patients with dilated cardiomyopathy (DCM) were previously analyzed, and the CHKB (choline kinase beta) divergent transcript (CHKB-DT) levels found to be mostly downregulated heart. In this study, function of CHKB-DT DCM was determined.

Язык: Английский

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Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Beyond the observed alterations in cellular structure and mitochondria, mechanisms linking rare genetic mutations to development of heart failure patients affected by desmin remain unclear due part, lack relevant human cardiomyocyte models.

Язык: Английский

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