Nano Today, Journal Year: 2022, Volume and Issue: 45, P. 101554 - 101554
Published: July 12, 2022
Language: Английский
Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 81, P. 101706 - 101706
Published: Aug. 4, 2022
Language: Английский
Citations
131
Nature, Journal Year: 2023, Volume and Issue: unknown
Published: Sept. 27, 2023
Abstract Postnatal maturation of cardiomyocytes is characterized by a metabolic switch from glycolysis to fatty acid oxidation, chromatin reconfiguration and exit the cell cycle, instating barrier for adult heart regeneration 1,2 . Here, explore whether reprogramming can overcome this enable regeneration, we abrogate oxidation in inactivation Cpt1b We find that disablement improves resistance hypoxia stimulates cardiomyocyte proliferation, allowing after ischaemia–reperfusion injury. Metabolic studies reveal profound changes energy metabolism accumulation α-ketoglutarate -mutant cardiomyocytes, leading activation α-ketoglutarate-dependent lysine demethylase KDM5 (ref. 3 ). Activated demethylates broad H3K4me3 domains genes drive maturation, lowering their transcription levels shifting into less mature state, thereby promoting proliferation. conclude shapes epigenetic landscape creating roadblock further divisions. Reversal process allows repair damaged hearts.
Language: Английский
Citations
130
Biomaterials, Journal Year: 2023, Volume and Issue: 296, P. 122088 - 122088
Published: March 6, 2023
Language: Английский
Citations
45
Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(4), P. 839 - 856.e8
Published: Feb. 16, 2024
Language: Английский
Citations
24
Nature Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 2, 2025
In contrast to adult mammalian hearts, the zebrafish heart efficiently replaces cardiomyocytes lost after injury. Here we reveal shared and species-specific injury response pathways a correlation between Hmga1, an architectural non-histone protein, regenerative capacity, as Hmga1 is required sufficient induce cardiomyocyte proliferation for regeneration. addition, was shown reactivate developmentally silenced genes, likely through modulation of H3K27me3 levels, poising them pro-regenerative gene program. Furthermore, AAV-mediated expression in injured mouse hearts led controlled border zone enhanced function, without cardiomegaly adverse remodeling. Histone modification mapping revealed similar marks, consistent with findings zebrafish. Our study demonstrates that mediates chromatin remodeling drives program, positioning it promising therapeutic target enhance cardiac regeneration Bouwman et al. identify Hmga1-mediated fundamental regulator potential restore repair mice by reactivating developmental suggesting applications.
Language: Английский
Citations
3
npj Regenerative Medicine, Journal Year: 2025, Volume and Issue: 10(1)
Published: Jan. 22, 2025
Myocardial infarction (MI) causes the loss of millions cardiomyocytes, and current treatments do not address this root issue. New therapies focus on stimulating cardiomyocyte division in adult heart, inspired by regenerative capacities lower vertebrates neonatal mice. This review explores strategies for heart regeneration, offers insights into proliferation, evaluates vivo models, discusses integrating vitro human cardiac models to advance regeneration research.
Language: Английский
Citations
2
International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6587 - 6587
Published: June 19, 2021
Citrate plays a central role in cancer cells’ metabolism and regulation. Derived from mitochondrial synthesis and/or carboxylation of α-ketoglutarate, it is cleaved by ATP-citrate lyase into acetyl-CoA oxaloacetate. The rapid turnover these molecules proliferative cells maintains low-level citrate, precluding its retro-inhibition on glycolytic enzymes. In relying glycolysis, this regulation helps sustain the Warburg effect. those an oxidative metabolism, fatty acid β-oxidation sustains high production which still rapidly converted oxaloacetate, latter molecule sustaining nucleotide gluconeogenesis. Therefore, citrate levels are rarely cells. Resistance to targeted therapies, such as tyrosine kinase inhibitors (TKIs), frequently sustained aerobic glycolysis key oncogenic drivers, Ras downstream effectors MAPK/ERK PI3K/Akt. Remarkably, preclinical models, administration doses showed various anti-cancer effects, inhibition promotion cytotoxic drugs sensibility apoptosis, neutralization extracellular acidity, tumors growth signalling pathways (in particular, IGF-1R/AKT pathway). results support testing strategy clinical trials counteract drivers development resistance therapies.
Language: Английский
Citations
93
Circulation Research, Journal Year: 2022, Volume and Issue: 131(6), P. 528 - 541
Published: Aug. 12, 2022
Background: Inhibiting SDH (succinate dehydrogenase), with the competitive inhibitor malonate, has shown promise in ameliorating ischemia/reperfusion injury. However, key for translation to clinic is understanding mechanism of malonate entry into cells enable inhibition SDH, its mitochondrial target, as itself poorly permeates cellular membranes. The possibility selectively entering at-risk heart tissue on reperfusion, however, remains unexplored. Methods: C57BL/6J mice, C2C12 and H9c2 myoblasts, HeLa were used elucidate selective uptake ischemic upon reperfusion. Cells treated while varying pH or together transport inhibitors. Mouse hearts either perfused ex vivo (Langendorff) subjected left anterior descending coronary artery ligation models Succinate levels assessed by liquid chromatography-tandem mass spectrometry LC-MS/MS, imaging, infarct size TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining. Results: Malonate was robustly protective against cardiac injury, but only if administered at reperfusion not when infused before ischemia. extent proportional duration cardiomyocytes vitro dramatically increased low (≈6.5) associated This blocked MCT1 (monocarboxylate transporter 1). Reperfusion region led region. Acid-formulation greatly enhances cardioprotective potency malonate. Conclusions: Cardioprotection dependent cardiomyocytes. facilitated local decrease that occurs during ischemia, leading tissue, via MCT1. Thus, malonate’s preferential reperfused means it an tissue-selective drug protects
Language: Английский
Citations
61
Redox Biology, Journal Year: 2022, Volume and Issue: 56, P. 102446 - 102446
Published: Aug. 23, 2022
Metabolic switching during heart development contributes to postnatal cardiomyocyte (CM) cell cycle exit and loss of regenerative capacity in the mammalian heart. control has potential for developing effective CM proliferation strategies. We sought determine whether lactate dehydrogenase A (LDHA) regulated by inducing metabolic reprogramming.LDHA expression was high P1 hearts significantly decreased development. CM-specific LDHA knockout mice were generated using CRISPR/Cas9 technology. inhibited proliferation, leading worse cardiac function a lower survival rate neonatal apical resection model. In contrast, overexpression promoted repair post-MI. The α-MHC-H2B-mCh/CAG-eGFP-anillin system used confirm proliferative effect triggered on P7 CMs adult hearts. Metabolomics, proteomics Co-IP experiments indicated that LDHA-mediated succinyl coenzyme reduction succinylation-dependent ubiquitination thioredoxin reductase 1 (Txnrd1), which alleviated ROS thereby proliferation. addition, flow cytometry western blotting showed LDHA-driven production created beneficial microenvironment M2 macrophage polarization.LDHA-mediated reprogramming alleviating polarization, indicating might be an target promoting
Language: Английский
Citations
57
Circulation, Journal Year: 2022, Volume and Issue: 145(17), P. 1339 - 1355
Published: Jan. 21, 2022
The regenerative capacity of the heart after myocardial infarction is limited. Our previous study showed that ectopic introduction 4 cell cycle factors (4F; CDK1 [cyclin-dependent kinase 1], CDK4 4], CCNB [cyclin B1], and CCND D1]) promotes cardiomyocyte proliferation in 15% to 20% infected cardiomyocytes vitro vivo improves cardiac function mice.
Language: Английский
Citations
56