Dataset Information

The Long Non-Coding RNA Landscape of Atherosclerotic Plaques.

ABSTRACT: Currently, cardiovascular diseases continue to be the leading cause of death worldwide; therefore, atherosclerosis remains one of the most crucial public health problems. This chronic and complex disease is considered to be a result of aberrant lipid homeostasis and inflammation of the inner wall of arteries that leads to plaque development. In recent years, a specific class of non-coding RNAs that are characterised by transcript lengths longer than 200 nucleotides, called long non-coding RNAs (lncRNAs), has emerged. Moreover, a growing body of evidence indicates that deregulation of lncRNA expression may contribute to the development of many diseases. Despite continuous efforts in deciphering the molecular basis of atherosclerotic plaque (AP) formation, many aspects of this process remain elusive. Therefore, continuing efforts in this area should remain the highest priority in the coming years. Establishment of a standardised experimental pipeline and validation of lncRNAs as possible relevant biomarkers for cardiovascular disease would enable the translation of gathered findings into clinical practice.

SUBMITTER: Kraczkowska W

PROVIDER: S-EPMC6879443 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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The Long Non-Coding RNA Landscape of Atherosclerotic Plaques.

Kraczkowska Weronika W Jagodziński Paweł Piotr PP

Molecular diagnosis & therapy 20191201 6

Currently, cardiovascular diseases continue to be the leading cause of death worldwide; therefore, atherosclerosis remains one of the most crucial public health problems. This chronic and complex disease is considered to be a result of aberrant lipid homeostasis and inflammation of the inner wall of arteries that leads to plaque development. In recent years, a specific class of non-coding RNAs that are characterised by transcript lengths longer than 200 nucleotides, called long non-coding RNAs ( ...[more]

PMID: 31602567

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Project description:BackgroundAtherosclerosis involves a slow process of plaque formation on the walls of arteries, and comprises a leading cause of cardiovascular disease. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of atherosclerosis. In this study, we aim to explore the possible involvement of lncRNA 'cyclin-dependent kinase inhibitor 2B antisense noncoding RNA' (CDKN2B-AS1) and CDKN2B in the progression of atherosclerosis.MethodsInitially, we quantified the expression of CDKN2B-AS1 in atherosclerotic plaque tissues and, in THP-1 macrophage-derived, and human primary macrophage (HPM)-derived foam cells. Next, we established a mouse model of atherosclerosis using apolipoprotein E knockout (ApoE-/-) mice, where lipid uptake, lipid accumulation, and macrophage reverse cholesterol transport (mRCT) were assessed, in order to explore the contributory role of CDKN2B-AS1 to the progression of atherosclerosis. RIP and ChIP assays were used to identify interactions between CDKN2B-AS1, CCCTC-binding factor (CTCF), enhancer of zeste homologue 2 (EZH2), and CDKN2B. Triplex formation was determined by RNA-DNA pull-down and capture assay as well as EMSA experiment.FindingsCDKN2B-AS1 showed high expression levels in atherosclerosis, whereas CDKN2B showed low expression levels. CDKN2B-AS1 accelerated lipid uptake and intracellular lipid accumulation whilst attenuating mRCT in THP-1 macrophage-derived foam cells, HPM-derived foam cells, and in the mouse model. EZH2 and CTCF were found to bind to the CDKN2B promoter region. An RNA-DNA triplex formed by CDKN2B-AS1 and CDKN2B promoter was found to recruit EZH2 and CTCF in the CDKN2B promoter region and consequently inhibit CDKN2B transcription by accelerating histone methylation.InterpretationThe results demonstrated that CDKN2B-AS1 promotes atherosclerotic plaque formation and inhibits mRCT in atherosclerosis by regulating CDKN2B promoter, and thereby could be a potential therapeutic target for atherosclerosis.

Dataset Information

The Long Non-Coding RNA Landscape of Atherosclerotic Plaques.

Publications

The Long Non-Coding RNA Landscape of Atherosclerotic Plaques.

Similar Datasets

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