Atrial fibrillation

Nature Reviews Disease Primers, Journal Year: 2022, Volume and Issue: 8(1)

Published: April 7, 2022

Atrial fibrillation (AF) is the most common cardiac arrhythmia despite substantial efforts to understand pathophysiology of condition and develop improved treatments. Identifying underlying causative mechanisms AF in individual patients difficult efficacy current therapies suboptimal. Consequently, incidence steadily rising there a pressing need for novel therapies. Research has revealed that defects specific molecular pathways underlie pathogenesis, resulting electrical conduction disorders drive AF. The severity this so-called electropathology correlates with stage disease progression determines response treatment. Therefore, unravelling expected fuel development innovative personalized diagnostic tools mechanism-based Moreover, co-creation studies implement prerequisite successful management. Currently, various treatment modalities targeting AF-related electropathology, including lifestyle changes, pharmaceutical nutraceutical therapy, substrate-based ablative neuromodulation, are available maintain sinus rhythm might offer holistic strategy treat increasing prevalence as populations age. This Primer provides an overview epidemiology, AF, approaches treatments, highlights important directions improve understanding management patients.

Language: Английский

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Mechanisms of microtubule organization in differentiated animal cells

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(8), P. 541 - 558

Published: April 5, 2022

Language: Английский

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The microtubule cytoskeleton in cardiac mechanics and heart failure

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 19(6), P. 364 - 378

Published: April 19, 2022

Language: Английский

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Posttranslational modification of microtubules by the MATCAP detyrosinase

Science, Journal Year: 2022, Volume and Issue: 376(6595)

Published: April 28, 2022

The detyrosination-tyrosination cycle involves the removal and religation of C-terminal tyrosine α-tubulin is implicated in cognitive, cardiac, mitotic defects. vasohibin-small vasohibin-binding protein (SVBP) complex underlies much, but not all, detyrosination. We used haploid genetic screens to identify an unannotated protein, microtubule associated carboxypeptidase (MATCAP), as a remaining detyrosinating enzyme. X-ray crystallography cryo-electron microscopy structures established MATCAP's cleaving mechanism, substrate specificity, recognition. Paradoxically, whereas abrogation lethal mice, codeletion MATCAP SVBP not. Although viable, defective detyrosination caused microcephaly, with proliferative defects during neurogenesis, abnormal behavior. Thus, missing component cycle, revealing importance this modification brain formation.

Language: Английский

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Triboelectric nanogenerators and piezoelectric nanogenerators for preventing and treating heart diseases

BMEMat, Journal Year: 2023, Volume and Issue: 1(2)

Published: April 15, 2023

Abstract Heart diseases pose a serious threat to human health, and their incidence has been increasing in recent years. In past decades, many strategies have developed decrease the mortality morbidity of heart diseases, among them, involving cardiac electronic devices (CEDs) effective treating preventing diseases. To allow CEDs work continuously without need replace batteries meet requirements convenience comfort process use, nanogenerator (NG)‐based were proposed, widely studied, optimized years owing advantages small dimensions, self‐powering ability, good biocompatibility. this review, improvements NG‐based two typical types (i.e., triboelectric [TENG] piezoelectric [PENG]) structures functions are summarized discussed. The demands, remaining challenges, future development trends also

Language: Английский

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Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 2, 2024

Abstract Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, contraction, making them valuable long-term repair. In this study, we find downregulated miR-199a-5p expression MI. Intramyocardial injection into the infarcted region male rats revealed its dual protective effects on heart. Specifically, targets AGTR1, diminishing early oxidative damage post-myocardial infarction, MARK4, which influences contractility enhances cardiac function. To deliver efficiently specifically to ischemic tissue, use CSTSMLKAC peptide construct P-MSN/miR199a-5p nanoparticles. Intravenous administration these nanoparticles reduces injury protects Our findings demonstrate effectiveness repairing through enhanced contraction anti-apoptosis. miR199a-5p holds significant therapeutic potential repair infarction.

Language: Английский

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Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration

Circulation, Journal Year: 2024, Volume and Issue: 151(1), P. 59 - 75

Published: Aug. 26, 2024

BACKGROUND: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, moves out of the nucleus. pathophysiological mechanisms regulating subcellular localization after myocardial infarction remain poorly defined. METHODS: We identified acetylation at site K265 by vitro followed mass spectrometry analysis. used adeno-associated virus express YAP-containing mutations that either abolished (YAP-K265R) or mimicked (YAP-K265Q) studied how regulates mouse hearts. generated a cell line with YAP-K265R mutation investigated protein-protein interactors immunoprecipitation spectrometry, then validated interaction neonatal rat ventricular myocytes. examined colocalization TUBA4A (tubulin α 4A) superresolution imaging. Furthermore, we developed αMHC-MerCreMer (MCM); Yap-loxP/K265R mutant mice examine cardiomyocytes during cardiac RESULTS: found is acetylated CBP (CREB-binding protein)/P300 (E1A-binding protein P300) deacetylated nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide/sirtuins axis cardiomyocytes. After infarction, increased, which promotes cytoplasmic localization. Compared controls, were genetically engineered K265R prevents showed improved regenerative ability increased nuclear Mechanistically, facilitates its TUBA4A, component microtubule network sequesters cytoplasm. cardiomyocytes, resulting accumulation CONCLUSIONS: decreased sirtuin activity enriches K265. growing within cytoplasm, detrimental

Language: Английский

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Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(41)

Published: Oct. 6, 2022

Heart failure (HF) is a leading cause of death and repeated hospitalizations often involves cardiac mitochondrial dysfunction. However, the underlying mechanisms largely remain elusive. Here, using mouse model in which myocardial infarction (MI) was induced by coronary artery ligation, we show metabolic basis dysfunction chronic HF. Four weeks after MI mice showed significant decrease succinyl-CoA levels, this impaired oxidative phosphorylation (OXPHOS) capacity. Heme synthesis ketolysis, protein levels several enzymes consuming these events, were increased mice, while synthesizing from α-ketoglutarate glutamate also increased. Furthermore, ADP-specific subunit synthase reduced, its GDP-specific almost unchanged. Administration 5-aminolevulinic acid, an intermediate pathway to heme synthesis, appreciably restored OXPHOS capacity prevented HF progression mice. Previous reports suggested presence metabolism abnormalities muscles patients. Our results identified that changes usage different metabolisms energy production system characteristic HF, although similar alterations are known occur healthy conditions, such as during strenuous exercise, they may irreversibly succinyl-CoA. Consequently, nutritional interventions compensating consumption expected be promising strategies treat

Language: Английский

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Promoting maturation and contractile function of neonatal rat cardiomyocytes by self-powered implantable triboelectric nanogenerator

Nano Energy, Journal Year: 2022, Volume and Issue: 103, P. 107798 - 107798

Published: Sept. 12, 2022

Cardiomyocyte-based therapeutic strategy is a promising approach to treat myocardial injury; however, the prognostic power of this currently limited by immaturity cardiomyocytes. Here, flexible self-powered implantable electrical stimulator based on triboelectric nanogenerator (TENG) was proposed induce maturation cardiomyocytes generating an electric field interdigitated electrode. The results showed that TENG-based significantly promoted neonatal rat (NRCMs) in vitro increasing expression connexin 43, α-actinin, and c-troponin T. In addition, stimulation also improved sarcomere organization fracture formation, increased intracellular Ca2+ levels, transient rate, peak amplitudes TENG shown be driven breath rats heartbeat rabbits, suggesting it could used as medical electronic device for electrically promoting This work develops device, which provides important technical support clinical treatment defects restoration physiological function cardiac tissue.

Language: Английский

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Investigating MARK4 inhibitory potential of Bacopaside II: Targeting Alzheimer's disease

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 245, P. 125364 - 125364

Published: June 13, 2023

Language: Английский

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