Insights into RNA N6-methyladenosine and programmed cell death in atherosclerosis DOI Creative Commons

Haijiao Long,

Yulu Yu,

Jie Ouyang

et al.

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: Sept. 3, 2024

Abstract N6-methyladenosine (m 6 A) modification stands out among various RNA modifications as the predominant form within eukaryotic cells, influencing numerous cellular processes implicated in disease development. m A has gained increasing attention development of atherosclerosis and become a research hotspot recent years. Programmed cell death (PCD), encompassing apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, plays pivotal role pathogenesis. In this review, we delve into intricate interplay between diverse PCD pathways, shedding light on their complex association during onset progression atherosclerosis. Clarifying relationship is great significance to provide novel strategies for cardiovascular treatment.

Language: Английский

Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease DOI Creative Commons
Bo Yu, Shusheng Wang

Theranostics, Journal Year: 2018, Volume and Issue: 8(13), P. 3654 - 3675

Published: Jan. 1, 2018

Long noncoding RNAs (lncRNAs) represent a large subgroup of that are longer than 200 nucleotides and have no apparent protein coding potential.They diverse functions in different biological processes by regulating chromatin remodeling or translation.This review summarizes the recent progress lncRNAs angiogenesis vascular diseases.A general overview lncRNA functional mechanisms will be introduced.A list lncRNAs, which termed "Angio-LncRs", including MALAT1, MANTIS, PUNISHER, MEG3, MIAT, SENCR GATA6-AS, discussed regarding their expression, regulation, function mechanism action angiogenesis.Implications diseases, such as atherosclerosis, hypertension, retinopathies tumor also discussed.

Language: Английский

Citations

174
Vascular mechanotransduction DOI
Michael J. Davis, Scott Earley,

Yi‐Shuan Li

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(2), P. 1247 - 1421

Published: Jan. 5, 2023

This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial (ECs), including their sensing mechanical stimuli transduction signals that result acute functional modulation longer-term transcriptomic epigenetic regulation blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures receptors, junction proteins. mechanosignaling pathways presented cytoskeleton, integrins, extracellular matrix, intracellular signaling molecules. These are followed by discussions on transcriptome epigenetics, relevance health disease, interactions between VSMCs ECs. Throughout this review, we offer suggestions for specific topics require further understanding. In closing section conclusions perspectives, summarize what is known point out need treat vasculature as a system, not only ECs but also matrix other types such resident macrophages pericytes, so can fully understand physiology pathophysiology vessel whole, thus enhancing comprehension, diagnosis, treatment, prevention diseases.

Language: Английский

Citations

107
ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease DOI Open Access
Liu Ouyang,

Xiaoyan Su,

Wenxin Li

et al.

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(14)

Published: May 18, 2021

Vascular calcification (VC) predicts cardiovascular morbidity and mortality in chronic kidney disease (CKD). To date, the underlying mechanisms remain unclear. We detected leukocyte DNA N6-methyladenine (6mA) levels patients with CKD or without aortic arch calcification. used arteries from mice infected vascular smooth muscle cell–targeted (VSMC-targeted) adeno-associated virus encoding alkB homolog 1 (Alkbh1) gene Alkbh1 shRNA to evaluate features of identified that 6mA were significantly reduced as severity VC increased CKD. Decreased demethylation resulted upregulation ALKBH1. Here, ALKBH1 overexpression aggravated whereas its depletion blunted progression osteogenic reprogramming vivo vitro. Mechanistically, ALKBH1-demethylated modification could facilitate binding octamer-binding transcription factor 4 (Oct4) bone morphogenetic protein 2 (BMP2) promoter activate BMP2 transcription. This VSMCs subsequent progression. Either Oct4 alleviated procalcifying effects suggests targeting might be a therapeutic method reduce burden

Language: Английский

Citations

59
Role of N6-methyladenosine modification in pathogenesis of ischemic stroke DOI

Hongtao Chang,

Yang Jun, Qianwen Wang

et al.

Expert Review of Molecular Diagnostics, Journal Year: 2022, Volume and Issue: 22(3), P. 295 - 303

Published: March 3, 2022

N6-Methyladenosine (m6A), the most common and reversible mRNA modification, has attracted considerable attention recently, accumulating evidence indicates it an important role in progression of ischemic stroke (IS).We first reviewed m6A methylation modification enzymes, including methyltransferases (METTL3, METTL14, WTAP), demethylases (FTO ALKBH5), m6A-binding proteins (YTH domain containing 1/2 [YTHDC1/2], YTHDF1/2/3, insulin like growth factor 2 binding protein 1/2/3 [IGF2BP1/2/3]), their-related functions. An alteration profile IS been reported is differentially expressed IS. Thus, we then focused on underlying mechanism involvement atherosclerosis (AS), cerebral ischemia/reperfusion (IR) injury, inflammation, oxidative stress, apoptosis. Furthermore, also elucidated effect m6A-associated single-nucleotide polymorphisms (SNPs) uncovered new causal variants for The clinical application targeting drugs still its infancy will be available future.Collectively, information present review a summary latest developments highlights mechanisms pathogenesis, which may provide novel insights into therapeutic targets

Language: Английский

Citations

46
Emerging Roles and Mechanism of m6A Methylation in Cardiometabolic Diseases DOI Creative Commons

Zujie Xu,

Binbin Lv,

Ying Qin

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(7), P. 1101 - 1101

Published: March 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

Language: Английский

Citations

42
Alkbh1‐mediated DNA N6‐methyladenine modification regulates bone marrow mesenchymal stem cell fate during skeletal aging DOI Creative Commons

Guangping Cai,

Yalin Liu, Liping Luo

et al.

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(2)

Published: Jan. 11, 2022

DNA N6-methyladenine (N6-mA) demethylase Alkbh1 participates in regulating osteogenic differentiation of mesenchymal stem cell (MSCs) and vascular calcification. However, the role bone metabolism remains unclear.Bone marrow cells (BMSCs)-specific knockout mice were used to investigate metabolism. Western blot, qRT-PCR, immunofluorescent staining evaluate expression or optineurin (optn). Micro-CT, histomorphometric analysis, calcein double-labeling assay phenotypes. Cell qRT-PCR adipogenic BMSCs. Dot blotting was detect level N6-mA genomic DNA. Chromatin immunoprecipitation (Chip) assays identify critical targets Alkbh1. adeno-associated virus overexpress aged mice.Alkbh1 BMSCs declined during aging. Knockout promoted while inhibited differentiation. BMSC-specific exhibited reduced mass increased adiposity. Mechanistically, we identified optn as downstream target through which Alkbh1-mediated m6A modification regulated fate. Overexpression attenuated loss fat accumulation mice.Our findings demonstrated that fate bone-fat balance skeletal aging provided a potential for treatment osteoporosis.

Language: Английский

Citations

40
Regulatory roles of N6-methyladenosine (m6A) methylation in RNA processing and non-communicable diseases DOI
Faiz Ali Khan, Bernard Nsengimana, Usman Ayub Awan

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: June 5, 2024

Language: Английский

Citations

9
Inhibition of the lncRNA MIAT prevents podocyte injury and mitotic catastrophe in diabetic nephropathy DOI Creative Commons
Ziyang Wang, Ying Chang, Yue Liu

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2022, Volume and Issue: 28, P. 136 - 153

Published: March 8, 2022

Podocyte damage is strongly associated with the progression of diabetic nephropathy. Mitotic catastrophe plays an essential role in accelerating podocyte loss and detachment from glomerular basement membrane. In current study, we observed that long non-coding RNA (lncRNA) MIAT was noticeably upregulated plasma kidney tissues patients nephropathy, this upregulation accompanied by higher albumin/creatinine ratios serum creatinine levels. By generating CRISPR-Cas9 Miat-knockout (KO) mice vivo employing vectors vitro, found depletion Miat expression significantly restored slit-diaphragm integrity, attenuated foot process effacement, prevented dedifferentiation, suppressed mitotic podocytes during hyperglycemia. The mechanistic investigation revealed increased Sox4 subsequently regulated p53 ubiquitination acetylation, thereby inhibiting downstream factors CyclinB/cdc2 enhancing p21cip1/waf1 activity, interacted sponging miR-130b-3p. Additionally, inhibition miR-130b-3p antagomir effectively enhanced injury dysfunction, eventually exacerbating proteinuria. Based on these findings, may represent a therapeutic target for

Language: Английский

Citations

30
N6-methyladenosine (m6A) methylation in ischemia–reperfusion injury DOI Creative Commons
Weifeng Yao, Xue Han, Mian Ge

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(6)

Published: June 24, 2020

Abstract Ischemia–reperfusion (I/R) injury is common during surgery and often results in organ dysfunction. The mechanisms of I/R are complex, diverse, not well understood. RNA methylation a novel epigenetic modification that involved the regulation various biological processes, such as immunity, response to DNA damage, tumorigenesis, metastasis, stem cell renewal, fat differentiation, circadian rhythms, development division. Research on modifications, specifically N6-methyladenosine (m 6 A), have confirmed they injury. In this review, we summarized current understanding regulatory roles significance m A different organs.

Language: Английский

Citations

49
DNA methylation and hydroxymethylation are associated with the degree of coronary atherosclerosis in elderly patients with coronary heart disease DOI
Dan Jiang, Min Sun,

Linna You

et al.

Life Sciences, Journal Year: 2019, Volume and Issue: 224, P. 241 - 248

Published: March 10, 2019

Language: Английский

Citations

40