Emerging Roles and Mechanism of m6A Methylation in Cardiometabolic Diseases

Cells, Год журнала: 2022, Номер 11(7), С. 1101 - 1101

Опубликована: Март 24, 2022

Cardiometabolic diseases (CMDs) are currently the leading cause of death and disability worldwide, their underlying regulatory mechanisms remain largely unknown. N6-methyladenosine (m6A) methylation, most common abundant epigenetic modification eukaryotic mRNA, is regulated by m6A methyltransferase, demethylase, binding protein, which affect transcription, cleavage, translation, degradation target mRNA. methylation plays a vital role in physiological pathological processes CMDs. In this review, we summarize played CMDs, including obesity, hypertension, pulmonary ischemic heart disease, myocardial hypertrophy, failure, atherosclerosis. We also describe that potentially involve participation such as those driving calcium homeostasis, circadian rhythm, lipid metabolism, autophagy, macrophage response, inflammation. its regulators expected to be targets for treatment

Язык: Английский

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The role of RNA m6A methylation in lipid metabolism

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Сен. 8, 2022

The m6A methylation is the most numerous modification of mRNA in mammals, coordinated by RNA methyltransferases, demethylases, and binding proteins. They change level their specific manner. has a significant impact on lipid metabolic regulation. “writer” METTL3/METTL14 “eraser” FTO can promote accumulation lipids various cells affecting decomposition synthesis lipids. “reader” YTHDF recognizes sites regulates target genes’ translation. Due to this function that metabolism, plays pivotal role diseases makes it great potential for therapy.

Язык: Английский

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RNA modification in cardiovascular disease: implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 27, 2023

Abstract Cardiovascular disease (CVD) is the leading cause of death in world, with a high incidence and youth-oriented tendency. RNA modification ubiquitous indispensable cell, maintaining cell homeostasis function by dynamically regulating gene expression. Accumulating evidence has revealed role aberrant expression CVD caused dysregulated modification. In this review, we focus on nine common modifications: N 6 -methyladenosine (m A), 1 5-methylcytosine 5 C), 7 -methylguanosine G), 4 -acetylcytosine (ac pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, modifications U34 tRNA wobble. We summarize key regulators their effects expression, such as splicing, maturation, transport, stability, translation. Then, based classification CVD, mechanisms which occurs progresses through are discussed. Potential therapeutic strategies, therapy, reviewed these mechanisms. Herein, some (such stroke peripheral vascular disease) not included due to limited availability literature. Finally, prospective applications challenges discussed for purpose facilitating clinical Moreover, look forward more studies exploring roles future, there substantial uncultivated areas be explored.

Язык: Английский

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RNA modification m ⁶ Am: the role in cardiac biology

Epigenetics, Год журнала: 2023, Номер 18(1)

Опубликована: Июнь 18, 2023

Epitranscriptomic modifications have recently emerged into the spotlight of researchers due to their vast regulatory effects on gene expression and thereby cellular physiology pathophysiology. N6,2'-O-dimethyladenosine (m6Am) is one most prevalent chemical marks RNA dynamically regulated by writers (PCIF1, METTL4) erasers (FTO). The presence or absence m6Am in affects mRNA stability, regulates transcription, modulates pre-mRNA splicing. Nevertheless, its functions heart are poorly known. This review summarizes current knowledge gaps about modification regulators cardiac biology. It also points out technical challenges lists currently available techniques measure m6Am. A better understanding epitranscriptomic needed improve our molecular regulations which may lead novel cardioprotective strategies.

Язык: Английский

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Epitranscriptomic regulation in fasting hearts: implications for cardiac health

RNA Biology, Год журнала: 2024, Номер 21(1), С. 1 - 14

Опубликована: Фев. 7, 2024

Cardiac tolerance to ischaemia can be increased by dietary interventions such as fasting, which is associated with significant changes in myocardial gene expression. Among the possible mechanisms of how expression may altered are epigenetic modifications RNA – epitranscriptomics. N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) two most prevalent mRNA. These methylations reversible regulated proteins called writers, erasers, readers, m6A-repelled proteins. We analysed 33 these epitranscriptomic regulators rat hearts after cardioprotective 3-day fasting using RT-qPCR, Western blot, targeted proteomic analysis. found that were changed on mRNA or protein levels hearts, including up-regulation both demethylases FTO ALKBH5. In accordance, decreased methylation (m6A+m6Am) detected cardiac total fasting. also identified Nox4 Hdac1 transcripts, play a role cytoprotective action ketone bodies produced during Furthermore, we investigated impact inhibiting ALKBH5 adult primary cardiomyocytes (AVCMs). Our findings indicate reduced hypoxic AVCMs isolated from rats. This study showed complex machinery around m6A m6Am might an important adaptation well-known intervention.

Язык: Английский

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The crosstalk among autophagy, apoptosis, and pyroptosis in cardiovascular disease

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Окт. 28, 2022

In recent years, the mechanism of cell death has become a hotspot in research on pathogenesis and treatment cardiovascular disease (CVD). Different modes, including autophagy, apoptosis, pyroptosis, are mosaic with each other collaboratively regulate process CVD. This review summarizes interaction crosstalk key pathways or proteins which play critical role entire CVD explores specific mechanisms. Furthermore, this paper assesses interrelationships among these three deaths reviews how they By understanding modes go together we can learn about CVD, will enable us to identify new targets for preventing, controlling, treating It not only reduce mortality but also improve quality life.

Язык: Английский

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N6-methyladenosine in macrophage function: a novel target for metabolic diseases

Trends in Endocrinology and Metabolism, Год журнала: 2022, Номер 34(2), С. 66 - 84

Опубликована: Дек. 29, 2022

Язык: Английский

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Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation

Aquatic Toxicology, Год журнала: 2024, Номер 269, С. 106884 - 106884

Опубликована: Март 2, 2024

Язык: Английский

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Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Март 14, 2024

Abstract Background Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation miRNA, which is involved various inflammatory diseases, often observed obesity. This study aimed investigate miR-192 lipopolysaccharide (LPS)-induced ALI mice and its mechanism dysregulation Methods Human tissues were obtained from patients (BMI ≥ 30.0 kg/m 2 ) control 18.5–24.9 ). An mouse model was established by feeding high-fat diet (HFD), followed intratracheal instillation LPS induce ALI. Pulmonary macrophages depleted through clodronate liposomes. The expression examined tissues, primary alveolar (AMs), macrophage cell line (MH-S) using RT-qPCR. m6A quantification RIP assays helped determine cause dysregulation. agomir antagomir used function MH-S cells. Bioinformatics dual-luciferase reporter gene explore downstream targets miR-192. Results In mice, depletion significantly alleviated tissue inflammation injury, regardless challenge. diminished during obesity further decreased with stimulation. Obesity-induced overexpression FTO modification pri-miR-192, inhibiting generation vitro, inhibition enhanced LPS-induced polarization M1 AKT/ NF-κB pathway, while suppressed these reactions. BIG1 confirmed as target miR-192, offset protective effects vivo, when overexpressed pulmonary extent improved upon Conclusions Our indicates that obesity-induced downregulation exacerbates promoting activation. Targeting provide new therapeutic avenues for obesity-associated Graphical

Язык: Английский

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Evolving Strategies for Use of Phytochemicals in Prevention and Long-Term Management of Cardiovascular Diseases (CVD)

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6176 - 6176

Опубликована: Июнь 4, 2024

This report describes major pathomechanisms of disease in which the dysregulation host inflammatory processes is a factor, with cardiovascular (CVD) as primary model, and reviews strategies for countermeasures based on synergistic interaction between various agents, including drugs generally regarded safe (GRAS) natural medical material (NMM), such Ginkgo biloba, spice phytochemicals, fruit seed flavonoids. The 15 well-defined CVD classes are explored particular emphasis extent to oxidative stressors associated ischemia-reperfusion tissue injury contribute symptoms. four categories pharmaceutical agents used prevention therapy CVD: statins, beta blockers (β-blockers), blood thinners (anticoagulants), aspirin, presented along their adverse effects. Analyses cellular molecular features drug- NMM-mediated cardioprotective provided context development human clinical application. Future directions evolving research described here will be particularly focused characterization manipulation calcium- calcineurin-mediated cascades signaling from cell surface receptors immune cells nucleus, emergence both protective pathological epigenetic that may modulated by synergistically-acting combinations phytochemicals interact promote reduces effective dosage thus (often) toxicity drugs.

Язык: Английский

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