ABCA1 mRNA and protein levels in M-CSF-activated macrophages from patients with arterial stenosis

Demina, E. P.; Miroshnikova, V. V.; Majorov, N. V.; Давыденко, В. В.; Schwarzman, A. L.

doi:10.1134/s1990519x13060035

Cited by 6 publications

(3 citation statements)

References 27 publications

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“…The ABCA1 activity is also regulated by the calpain-mediated proteolytic degradation of the ABCA1 protein [29]. In other studies, the level of ABCA1 mRNA was also decreased in macrophages of patients with atherosclerosis, and the content of ABCA1 was decreased [30,31]. The authors suggested that the level of ABCA1 mRNA and the level of ABCA1 in macrophages may be essential factors in the development of atherosclerosis.…”

Section: Expression Changes In Atherosclerosismentioning

confidence: 89%

Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis

Rozhkova

Дмитриева

Nosova

et al. 2021

JCDD

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Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of ABCA1, ABCG1, and SCARB1, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review.

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Section: Expression Changes In Atherosclerosismentioning

confidence: 89%

Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis

Rozhkova

Дмитриева

Nosova

et al. 2021

JCDD

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“…In previous studies, ABCG1 has been shown to be hypermethylated and downregulated in blood monocytes/macrophages of CAD patients [ 24 , 41 , 43 ]. Furthermore, ABCA1 mRNA levels are upregulated in macrophages, while protein levels are decreased [ 44 , 45 ]. As adipose tissue is a complex tissue composed of different cell subsets, including macrophages, it may be hypothesized that EAT macrophages are critical for atherosclerotic plaques formation in the nearby coronary artery pool.…”

Section: Discussionmentioning

confidence: 99%

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease

Miroshnikova

Пантелеева

Pobozheva

et al. 2021

BMC Cardiovasc Disord

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Background Recent studies have focused on the potential role of epicardial adipose tissue (EAT) in the development of coronary artery disease (CAD). ABCA1 and ABCG1 transporters regulate cell cholesterol content and reverse cholesterol transport. We aimed to determine whether DNA methylation and mRNA levels of the ABCA1 and ABCG1 genes in EAT and subcutaneous adipose tissue (SAT) were associated with CAD. Methods Paired EAT and SAT samples were collected from 82 patients undergoing elective cardiac surgery either for coronary artery bypass grafting (CAD group, N = 66) or valve surgery (NCAD group, N = 16). ABCA1 and ABCG1 mRNA levels in EAT and SAT samples were analyzed using real time polymerase chain reaction, ABCA1 protein levels in EAT samples were assessed by western blotting. ABCA1 and ABCG1 DNA methylation analysis was performed in 24 samples from the CAD group and 9 samples from the NCAD group via pyrosequencing. Results DNA methylation levels in the ABCA1 promoter and ABCG1 cg27243685 and cg06500161 CpG sites were higher in EAT samples from patients with CAD compared with NCAD (21.92% vs 10.81%, p = 0.003; 71.51% vs 68.42%, p = 0.024; 46.11% vs 37.79%, p = 0.016, respectively). In patients with CAD, ABCA1 and ABCG1 DNA methylation levels were higher in EAT than in SAT samples (p < 0.05). ABCA1 mRNA levels in EAT samples were reduced in the subgroup of patients with CAD and concomitant carotid artery disease or peripheral artery disease compared with the NCAD group (p = 0.024). ABCA1 protein levels in EAT samples tended to be lower in CAD patients than in the NCAD group (p = 0.053). DNA methylation levels at the ABCG1 cg27243685 site positively correlated with plasma triglyceride concentration (r = 0.510, p = 0.008), body mass index (r = 0.556, p = 0.013) and waist-to-hip ratio (r = 0.504, p = 0.012) in SAT samples. Conclusion CAD is associated with ABCA1 and ABCG1 DNA hypermethylation in EAT. CAD with concomitant carotid artery disease or peripheral artery disease is accompanied by decreased ABCA1 gene expression in EAT. DNA methylation levels at the ABCG1 cg27243685 locus in SAT are associated with hypertriglyceridemia and obesity.

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“…Our results were consistent with the following reports. Demina et al cultured macrophages from patients with artery stenosis and healthy controls for 5 days in vitro and found that the mRNA expression of ABCA1 in macrophages of patients was signi cantly higher than controls (P<0.05) (Demina EP et al, 2013). Albrecht et al analyzed the mRNA expression of ABCA1 in atherosclerotic plaques of patients undergoing carotid endarterectomy (CEA) and normal arteries, and found that the mRNA expression of ABCA1 in atherosclerotic plaques was signi cantly increased (P<0.05) (Albrecht C et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation and SNPs of ABCA1 Gene Promoter Affect Gene Expression and Involve in the Pathological Mechanism of Ischemic Stroke

Wang²,

Zhou

et al. 2021

Preprint

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ATP binding cassette subfamily A1 (ABCA1) is a key protein in the formation of mature high density lipoprotein (HDL), which plays a crucial role in atherosclerosis. Accumulating evidence has shown that the expression levels of the ABCA1 gene are upregulated in ischemic stroke (IS) patients. However, the mechanism remains elusive. We hypothesized that DNA methylation and SNPs of ABCA1 gene promoter affect the expression levels of ABCA1 gene and involve in the pathological mechanism of IS. 100 patients with IS and 100 healthy controls were enrolled in the present study. Initially, the mRNA expression levels of ABCA1 gene were examined by qPCR and the methylation levels was detected by MethyTarget sequencing. Then, rs1800976, rs1800977, rs2246298, rs2437817, rs2740483, rs539621172 in promoter region of ABCA1 gene were selected for genotyping. Finally, the relationship between the methylation of ABCA1 gene and gene expression was verified by constructing THP-1 foam cell model. The mRNA expression levels of ABCA1 gene in the IS group were significantly higher than those in controls (P<0.05). 17 CpG sites in the promoter of ABCA1 gene were analyzed and the DNA methylation levels of CpG1, CpG7 and CpG15 sites in IS group was significantly lower than control group (P<0.05). Rs2740483, rs1800977 and rs2437817 were significantly correlated with CpG1. Rs1800977 was significantly correlated with CpG3. In summary, DNA methylation and rs2740483, rs1800977, rs2437817 of ABCA1 gene promoter affect the expression levels of ABCA1 gene, change the clearance rate of intracellular lipids, and participate in the pathogenesis of IS.

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ABCA1 mRNA and protein levels in M-CSF-activated macrophages from patients with arterial stenosis

Cited by 6 publications

References 27 publications

Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis

Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis

ABCA1 and ABCG1 DNA methylation in epicardial adipose tissue of patients with coronary artery disease

DNA Methylation and SNPs of ABCA1 Gene Promoter Affect Gene Expression and Involve in the Pathological Mechanism of Ischemic Stroke

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