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ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE192940 | GEO | 2024/12/01

REPOSITORIES: GEO

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ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ABCA1 RNA-seq]

Project description:Enhancer RNAs (eRNAs) are emerging as powerful regulators of various biological processes, but the underlying epigenetic regulatory mechanisms of these molecules in cholesterol homeostasis remain elusive. Using an integrated genomic screen, we identified an intragenic super-enhancer derived long noncoding RNA embedded in the ATP-binding cassette transporter A1 (ABCA1) gene, named ABCA1-seRNA, which is required for activation of RXRα/LXR mediated gene expression. Deficiency of ABCA1-seRNA abolished cholesterol efflux, promotes Macrophage Inflammation, and that haven been causally Susceptibility to Coronary heart disease. Mechanistically, ABCA1-seRNA affects cholesterol efflux by interaction with MED23 and recruitment RXR and LXR to mediate ABCA1 transcription in cis. Furthermore, ABCA1-seRNA repression inflammatory response and attenuated macrophage M1 polarization and migration through ubiquitination of a NF-B subunit P65. Our results suggest that super-enhancer derived long noncoding RNA, as a novel Epigenetic Regulator, are critical components to maintain cholesterol homeostasis and inflammation restriction, represent an attractive therapeutic target to reduce Atherosclerotic cardiovascular disease (ASCVD).

2024-12-01 | GSE192939 | GEO

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ATAC-seq]

2024-12-01 | GSE192936 | GEO

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [CUT&TAG]

2024-12-01 | GSE192937 | GEO

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [MED23 RNA-seq]

2024-12-01 | GSE192938 | GEO

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease

Project description:ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease

| PRJNA793850 | ENA

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ABCA1 RNA-seq]

Project description:ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ABCA1 RNA-seq]

| PRJNA793851 | ENA

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ATAC-seq]

Project description:ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [ATAC-seq]

| PRJNA793854 | ENA

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [CUT&TAG]

Project description:ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [CUT&TAG]

| PRJNA793853 | ENA

ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [MED23 RNA-seq]

Project description:ABCA1-eRNA as a novel Epigenetic Regulator, promotes cholesterol efflux, Attenuates Macrophage Inflammation and Severity of Coronary Artery Disease [MED23 RNA-seq]

| PRJNA793852 | ENA

TRAK2, a novel regulator of ABCA1 expression, cholesterol efflux and HDL biogenesis.

Project description:AimsThe recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration.Methods and resultsAnalysis of lymphocyte transcriptomic data together with plasma HDL from the San Antonio Family Heart Study (n?=?1240) revealed a significant negative correlation between TRAK2 mRNA levels and HDL-C concentration, HDL particle diameter and HDL subspecies heterogeneity. TRAK2 siRNA-mediated knockdown significantly increased cholesterol efflux to apolipoprotein A-I and isolated HDL from human macrophage (THP-1) and liver (HepG2) cells by increasing the mRNA and protein expression of the cholesterol transporter ATP-binding cassette, sub-family A member 1 (ABCA1). The effect of TRAK2 knockdown on cholesterol efflux was abolished in the absence of ABCA1, indicating that TRAK2 functions in an ABCA1-dependent efflux pathway. TRAK2 knockdown significantly increased liver X receptor (LXR) binding at the ABCA1 promoter, establishing TRAK2 as a regulator of LXR-mediated transcription of ABCA1.ConclusionWe show, for the first time, that TRAK2 is a novel regulator of LXR-mediated ABCA1 expression, cholesterol efflux, and HDL biogenesis. TRAK2 may therefore be an important target in the development of anti-atherosclerotic therapies.

| S-EPMC6251650 | biostudies-literature

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