scholarly journals Epigenetic Regulation in Pathology of Atherosclerosis: A Novel Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Haishuang Tang ◽  
Zhangwei Zeng ◽  
Chenghao Shang ◽  
Qiang Li ◽  
Jianmin Liu

Atherosclerosis, characterized by atherosclerotic plaques, is a complex pathological process that involves different cell types and can be seen as a chronic inflammatory disease. In the advanced stage, the ruptured atherosclerotic plaque can induce deadly accidents including ischemic stroke and myocardial infarction. Epigenetics regulation, including DNA methylation, histone modification, and non-coding RNA modification. maintains cellular identity via affecting the cellular transcriptome. The epigenetic modification process, mediating by epigenetic enzymes, is dynamic under various stimuli, which can be reversely altered. Recently, numerous studies have evidenced the close relationship between atherosclerosis and epigenetic regulations in atherosclerosis, providing us with a novel perspective in researching mechanisms and finding novel therapeutic targets of this serious disease. Here, we critically review the recent discoveries between epigenetic regulation mechanisms in atherosclerosis.

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1711 ◽  
Author(s):  
Conor P. Duffy ◽  
Claire E. McCoy

Multiple sclerosis (MS) is an autoimmune disorder characterised by demyelination of central nervous system neurons with subsequent damage, cell death and disability. While mechanisms exist in the CNS to repair this damage, they are disrupted in MS and currently there are no treatments to address this deficit. In recent years, increasing attention has been paid to the influence of the small, non-coding RNA molecules, microRNAs (miRNAs), in autoimmune disorders, including MS. In this review, we examine the role of miRNAs in remyelination in the different cell types that contribute to MS. We focus on key miRNAs that have a central role in mediating the repair process, along with several more that play either secondary or inhibitory roles in one or more aspects. Finally, we consider the current state of miRNAs as therapeutic targets in MS, acknowledging current challenges and potential strategies to overcome them in developing effective novel therapeutics to enhance repair mechanisms in MS.


Author(s):  
Esther Lutgens ◽  
Marie-Luce Bochaton-Piallat ◽  
Christian Weber

Atherosclerosis is a lipid-driven, chronic inflammatory disease of the large and middle-sized arteries that affects every human being and slowly progresses with age. The disease is characterized by the presence of atherosclerotic plaques consisting of lipids, (immune) cells, and debris that form in the arterial intima. Plaques develop at predisposed regions characterized by disturbed blood flow dynamics, such as curvatures and branch points. In the past decades, experimental and patient studies have revealed the role of the different cell-types of the innate and adaptive immune system, and of non-immune cells such as platelets, endothelial, and vascular smooth muscle cells, in its pathogenesis. This chapter highlights the roles of these individual cell types in atherogenesis and explains their modes of communication using chemokines, cytokines, and co-stimulatory molecules.


Author(s):  
Oza Zaheed ◽  
Stephen J. Kiniry ◽  
Pavel V. Baranov ◽  
Kellie Dean

Detection of translation in so-called non-coding RNA provides an opportunity for identification of novel bioactive peptides and microproteins. The main methods used for these purposes are ribosome profiling and mass spectrometry. A number of publicly available datasets already exist for a substantial number of different cell types grown under various conditions, and public data mining is an attractive strategy for identification of translation in non-coding RNAs. Since the analysis of publicly available data requires intensive data processing, several data resources have been created recently for exploring processed publicly available data, such as OpenProt, GWIPS-viz, and Trips-Viz. In this work we provide a detailed demonstration of how to use the latter two tools for exploring experimental evidence for translation of RNAs hitherto classified as non-coding. For this purpose, we use a set of transcripts with substantially different patterns of ribosome footprint distributions. We discuss how certain features of these patterns can be used as evidence for or against genuine translation. During our analysis we concluded that the MTLN mRNA, previously misannotated as lncRNA LINC000116, likely encodes only a short proteoform expressed from shorter RNA transcript variants.


2019 ◽  
Vol 1 (1) ◽  
pp. H67-H73
Author(s):  
Xuechong Hong ◽  
Wenduo Gu

Vascular remodeling is a complex and dynamic pathological process engaging many different cell types that reside within the vasculature. Mesenchymal stromal/stem cells (MSCs) refer to a heterogeneous cell population with the plasticity to differentiate toward multiple mesodermal lineages. Various types of MSC have been identified within the vascular wall that actively contribute to the vascular remodeling process such as atherosclerosis. With the advances of genetic mouse models, recent findings demonstrated the crucial roles of MSCs in the progression of vascular diseases. This review aims to provide an overview on the current knowledge of the characteristics and behavior of vascular resident MSCs under quiescence and remodeling conditions, which may lead to the development of novel therapeutic approaches for cardiovascular diseases.


2020 ◽  
Vol 21 (8) ◽  
pp. 2863 ◽  
Author(s):  
Maria L. Perepechaeva ◽  
Alevtina Y. Grishanova

Primary brain tumors, both malignant and benign, are diagnosed in adults at an incidence rate of approximately 23 people per 100 thousand. The role of AhR in carcinogenesis has been a subject of debate, given that this protein may act as either an oncogenic protein or a tumor suppressor in different cell types and contexts. Lately, there is growing evidence that aryl hydrocarbon receptor (AhR) plays an important part in the development of brain tumors. The role of AhR in brain tumors is complicated, depending on the type of tumor, on ligands that activate AhR, and other features of the pathological process. In this review, we summarize current knowledge about AhR in relation to brain tumors and provide an overview of AhR’s potential as a therapeutic target.


2019 ◽  
Author(s):  
Wanassa Beroual ◽  
David Lalaouna ◽  
Nadia Ben Zaina ◽  
Odile Valette ◽  
Karine Prévost ◽  
...  

SummaryBacterial cells are powerful models for understanding how cells divide and accomplish global regulatory programs. In Caulobacter crescentus a cascade of essential master regulators regulate the correct and sequential activation of DNA replication, cell division and development of different cell types. Among them CtrA plays a crucial role coordinating all those functions. Despite decades of investigation, no control by non-coding RNAs (ncRNAs) has been linked to Caulobacter cell cycle. Here, for the first time we describe the role of a novel essential factor named CcnA, a ncRNA located at the origin of replication, activated by CtrA and responsible for the rapid and strong accumulation of CtrA itself. In addition CcnA is also responsible for the inhibition of GcrA translation by direct interaction with its UTR region. By a combination of probing experiments and mutagenesis, we propose a new mechanism by liberation (CtrA) or sequestration (GcrA) of the Ribosome Binding Site (RBS). CcnA role is conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a conserved and fundamental process regulating cell cycle in Rhizobiales and Caulobacterales.


2021 ◽  
Vol 11 ◽  
Author(s):  
Erminia Rubino ◽  
Melania Cruciani ◽  
Nicolas Tchitchek ◽  
Anna Le Tortorec ◽  
Antoine D. Rolland ◽  
...  

Ubiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of IFN-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here, we identified microRNAs (miRNAs) that efficiently target USP18 through binding to the 3’untranslated region (3’UTR). Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baseline USP18. Intriguingly, the USP18 3’UTR sequence is duplicated in human and chimpanzee genomes. In humans, four USP18 3’UTR copies were previously found to be embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and known as FAM247A-D. Here, we further characterized their sequence and measured their expression profile in human tissues. Importantly, we describe an additional lincRNA bearing USP18 3’UTR (here linc-UR-B1) that is expressed only in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation between linc-UR-B1 and USP18 expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.


Author(s):  
Luca Braga ◽  
Hashim Ali ◽  
Ilaria Secco ◽  
Mauro Giacca

Abstract Abstract A growing body of evidence indicates that cardiac regeneration after myocardial infarction can be achieved by stimulating the endogenous capacity of cardiomyocytes (CMs) to replicate. This process is controlled, both positively and negatively, by a large set of non-coding RNAs (ncRNAs). Some of the microRNAs (miRNAs) that can stimulate CM proliferation is expressed in embryonic stem cells and is required to maintain pluripotency (e.g. the miR-302∼367 cluster). Others also govern the proliferation of different cell types, including cancer cells (e.g. the miR-17∼92 cluster). Additional miRNAs were discovered through systematic screenings (e.g. miR-199a-3p and miR-590-3p). Several miRNAs instead suppress CM proliferation and are involved in the withdrawal of CMs from the cell cycle after birth (e.g. the let-7 and miR-15 families). Similar regulatory roles on CM proliferation are also exerted by a few long ncRNAs. This body of information has obvious therapeutic implications, as miRNAs with activator function or short antisense oligonucleotides against inhibitory miRNAs or lncRNAs can be administered to stimulate cardiac regeneration. Expression of miRNAs can be achieved by gene therapy using adeno-associated vectors, which transduce CMs with high efficiency. More effective and safer for therapeutic purposes, small nucleic acid therapeutics can be obtained as chemically modified, synthetic molecules, which can be administered through lipofection or inclusion in lipid or polymer nanoparticles for efficient cardiac delivery. The notion that it is possible to reprogramme CMs into a regenerative state and that this property can be enhanced by ncRNA therapeutics remains exciting, however extensive experimentation in large mammals and rigorous assessment of safety are required to advance towards clinical application.


Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.


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