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Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular disease. 8-Hydroxyeicosapentaenoic acid (8-HEPE) from North Pacific krill (Euphausia pacifica) is known to reduce plasma low-density lipoprotein (LDL) cholesterol levels and increase plasma high-density lipoprotein cholesterol levels in LDL receptor knock-out mice fed a western diet. Moreover, 8-HEPE also reduces the area of aortic atherosclerosis in apoE knock-out mice fed the same diet. In this study, we examined the stereochemical-specific activity of 8-HEPE for inducing expression of cholesterol efflux receptors (Abca1 and Abcg1) in J774.1 cells. Our findings show 8R-HEPE induces the expression of Abca1 and Abcg1 via activation of liver X receptor, whereas 8S-HEPE elicits no such activity. These results suggest that 8R-HEPE derived from North Pacific krill may have beneficial effects against dyslipidemia. [ABSTRACT FROM AUTHOR]

ABCG1 is an essential protein involved in the efflux of intracellular cholesterol to the extracellular space, thus playing a critical role in reducing cholesterol accumulation in neighboring tissues. Bibliometric analysis pertains to the interdisciplinary field of quantitative examination of diverse documents using mathematical and statistical techniques. It integrates the investigation of structural and temporal patterns in academic publications with an exploration of subject focus and forms of uncertainty. This research paper examines the historical evolution, current areas of interest, and future development trends of ABCG1 through bibliometric analysis. This study aims to offer readers insights into the research status and emerging trends of ABCG1, thereby assisting researchers in the exciting field to explore novel research avenues. Following rigorous selection, research on ABCG1 has remained highly active over the past two decades. ABCG1 has even started to emerge in previously unrelated fields, such as the field of cancer research. According to the analysis conducted by Citespace, a lot of keywords and influential citations were identified. ABCG1 has been found to establish a connection between cancer and cardiovascular disease, highlighting their interrelationship. This review aims to assist readers who have limited familiarity with ABCG1 research in gaining a rapid understanding of its developmental trajectory. Additionally, it aims to offer researchers potential areas of focus for future studies related to ABCG1. [ABSTRACT FROM AUTHOR]

Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXR β agonists. A novel benzofuran-2-carboxylate derivative was identified with LXR β agonist activity: E17110 showed a significant activation effect on LXR β with an EC 50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXR β ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXR β agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound. [ABSTRACT FROM AUTHOR]

Background The adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1), a member of the superfamily of ATP-binding cassette transporters, is involved in the transport of cholesterol and phospholipids in macrophages. As such, ABCG1 plays a crucial role in the development of atherosclerosis in humans. In this study, we investigate the association between ABCG1 polymorphisms and the risk of developing ischemic stroke in a Chinese Han population. Methods This case–control study included 389 ischemic stroke patients and 380 healthy subjects. ABCG1 rs1378577 and rs57137919 polymorphisms were analyzed by a polymerase chain reaction-ligation detection reaction. Results We found that the genotypic distribution and allelic frequency of these polymorphisms were similar in patients and controls. In a subgroup with hypertriglyceridemia (144 patients and 115 controls), the frequency of rs1378577 GG genotype and G allele as well as rs57137919 AA genotype was lower in the patient group compared with that in the control group ( P = .018, P = .035, and P = .023, respectively). Logistic regression analysis revealed a reduced risk of ischemic stroke in a recessive model for both rs1378577 and rs57137919. Subtype analyses demonstrated that rs1378577 TG and GG genotypes and the G allele were associated with reduced risk of atherothrombotic stroke ( P = .030, P = .006, and P = .004, respectively), even after adjusting for confounding factors in a dominant model. Conclusions Data from the present study demonstrate that ABCG1 polymorphisms are associated with reduced risk of developing ischemic stroke in hypertriglyceridemic population and atherothrombotic stroke in this cohort of Chinese Han population. [ABSTRACT FROM AUTHOR]

The article discusses a research which examines the association between genomewide DNA methylation and blood lipid levels. It shows that lipid-related CpG site cg06500161, located in gene ABCG1, was associated in opposite directions with both high-density lipoprotein cholesterol and triglyceride levels. It reveals that epigenetic modifications of genetic loci contribute to the development of complex lipid-related diseases.

Abstract: Introduction: Transplacental feto-maternal lipid exchange through the ATP-binding cassette transporters ABCA1 and ABCG1 is important for normal fetal development. However, only scarce and conflicting data exist on the involvement of these transporters in gestational disease. Methods: Placenta samples (n = 72) derived from common gestational diseases, including pre-eclampsia (PE), HELLP, intrauterine growth restriction (IUGR), intrahepatic cholestasis of pregnancy and gestational diabetes, were assessed for their ABCA1 and ABCG1 expression levels and compared to age-matched control placentas with qRT-PCR and immunohistochemistry. ABCA1 expression was additionally investigated with immunoblot in placental membrane vesicles. Furthermore, placental cholesterol and phospholipid contents were assessed. Results: ABCA1 mRNA levels differed significantly between preterm and term control placentas (p = 0.0013). They were down-regulated in isolated PE and PE with IUGR (p = 0.0006 and p = 0.0012, respectively), but unchanged in isolated IUGR, isolated HELLP and other gestational diseases compared to gestational age-matched controls. Correspondingly, in PE, ABCA1 protein expression was significantly reduced in the apical membrane of the villous syncytiotrophoblast (p = 0.011) and in villous fetal endothelial cells (p = 0.036). Furthermore, in PE there was a significant increase in the placental content of total and individual classes of phospholipids which were partially correlated with diminished ABCA1 expression. Conversely, ABCG1 mRNA and protein levels were stable in the investigated conditions. Conclusions: In gestational disease, there is a specific down-regulation of placental ABCA1 expression at sites of feto-maternal lipid exchange in PE. At a functional level, the increase in placental lipid concentrations provides indirect evidence of an impaired transport capacity of ABCA1 in this disease. [Copyright &y& Elsevier]

Background: Homozygous familial hypercholesterolemia (FH) is a rare disorder that may affect 1 person per million. Early initiation of aggressive cholesterol-lowering therapy is essential to prevent premature coronary heart disease. Selective removal of low-density lipoprotein (LDL) by LDL apheresis is a reliable method of treatment. Methods and Results: Cholesterol efflux mediators of homozygous FH patients on weekly LDL apheresis were compared with those of age- and sex-matched heterozygous FH patients receiving oral medication only and with healthy control subjects. The data show that (1) compared with healthy controls, homozygous FH patients have significantly lower plasma levels of high-density lipoprotein cholesterol and apoA-I and significantly lower cholesterol-acceptor capacity of serum to promote cholesterol efflux from cholesterol-loaded THP-1 cells, combined with significantly lower peripheral blood mononuclear cell gene expression levels of ATP-binding cassette (ABC) transporter G1 and borderline-significantly lower levels of ABCA1 and scavenger receptor class B type I (SR-BI); and (2) compared with pre-LDL apheresis (a day before treatment), postapheresis (15 days later; on the day after the weekly treatment) levels of HDL cholesterol and apoA-I were significantly reduced, with no significant effect on cholesterol-acceptor capacity of serum or on peripheral blood mononuclear cell gene expression levels of the cellular transporters, except for a borderline-significant reduction in ABCA1 mRNA levels. Conclusions: The data showing decreased levels of cholesterol efflux mediators in plasma and cells may suggest that the overall cholesterol efflux capacity is impaired in homozygous FH patients. However, LDL apheresis may maintain cholesterol efflux capacity, despite a lowering levels of high-density lipoprotein cholesterol and apoA-I. [Copyright &y& Elsevier]

The article investigates the role of high-density lipoprotein (HDL) and adenosine triphosphate (ATP)-binding cassette transporters ABCA1 and ABCG1 in modulating the chemotaxis of macrophages. It is noted that these two ATP-binding cassette transporters facilitate macrophage chemotaxis by promoting plasma membrane (PM) transbilayer cholesterol movement. Deletion of both results to an increased cholesterol content on the inner leaflet of the PM, associated with increased Racl PM localization, activation, and impairment of migration.

Abstract: High-density lipoprotein (HDL) is proposed to inhibit atherosclerosis via a number of different pathways, including promotion of reverse cholesterol transport and inhibition of inflammation. However, studies in both mice and humans suggest that quantifying HDL-cholesterol (HDL-C) levels provide limited information regarding the cardioprotective effects of HDL. This article briefly reviews current thinking regarding the functional and cardioprotective effects of HDL and the role of the HDL proteome in these processes. [ABSTRACT FROM AUTHOR]

The losartan metabolite EXP3174 exhibits angiotensin II receptor 1 (AT1R)-blocking properties, whereas the metabolite EXP3179 potently induces the activity of the insulin-sensitizing peroxisome proliferator-activated receptor gamma (PPARgamma) as a partial agonist in vitro. We investigated whether chronic treatment with losartan leads to sufficient serum levels of EXP3179 to activate PPARgamma in monocytes derived from losartan-treated patients. Hypertensive patients (n=15) treated with losartan (100 mg/daily for at least the past 2 months) and untreated control patients (n=7) were included. Monocytes were extracted by negative isolation using a Dynal Monocyte Kit, followed by analysis of PPARgamma target gene expression (CD36, ABC transporter G1 [ABCG1]) by quantitative real-time RT-PCR. Serum was prepared before, 2, 4, and 6 hours after losartan (100 mg) ingestion for HPLC-based determination of losartan, EXP3174, and EXP3179. Chronic treatment with losartan resulted in basal levels of losartan, EXP3174, and EXP3179 of 348.3+/-101.8 ng/mL, 115.3+/-56.1 ng/mL, and 176.2+/-143.4 ng/mL, respectively. Levels of both EXP3174 and EXP3179 were time-dependently increased in serum with a maximum 2 hours after drug intake (1706.0+/-760.1 ng/mL, 808.9+/-618.2 ng/mL, respectively). In consonance with detectable PPARgamma-activating EXP3179 serum levels, monocytic PPARgamma target gene expression was significantly upregulated in patients treated with losartan by 3.75+/-0.95- and 252.02+/-46.86-fold for CD36 and ABCG1 (P=0.043, P=0.0045 versus control patients, respectively). This is the first clinical description of monocytic PPARgamma-target gene regulation by chronic treatment with losartan, which likely is mediated by its metabolite EXP3179. Our data show that sufficient serum levels of EXP3179 are present under losartan treatment. PPARgamma activation by AT1R-blockers may translate into synergistic beneficial actions in monocytes. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Monounsaturated fatty acids in diets are beneficial for the plasma lipoprotein profile, but studies in cell culture point out that they may also be detrimental by inhibiting cholesterol efflux to apo AI. Methods and Results: In the present study we used mouse peritoneal macrophages, loaded with cholesterol and upregulated by cyclic AMP or by LXR/RXR ligands and compared the effect of oleic acid on cholesterol efflux to 3 different acceptors. Inhibition of cholesterol efflux by oleic acid ranged from 10 to 25% with HDL or 2.5% mouse serum, while efflux to phosphatidyl choline vesicles was not affected. Previously we reported that the LXR ligand, TO901317, retarded cholesterol removal in vivo from a modified LDL depot in muscle. This could have resulted from inhibition by unsaturated fatty acids or from reduction in macrophage recruitment due to the anti-inflammatory action of LXR. Conclusions: Our current findings, of retardation of cholesterol clearance from the depot in the presence of low macrophage recruitment, support the latter possibility. [Copyright &y& Elsevier]

Adipogenesis is critical for adipose tissue remodeling during the development of obesity. While the role of transcription factors in the orchestration of adipogenic pathways is already established, the involvement of coregulators that transduce regulatory signals into epigenome alterations and transcriptional responses remains poorly understood. The aim of our study was to investigate which pathways are controlled by G protein pathway suppressor 2 (GPS2) during the differentiation of human adipocytes. We generated a unique loss-of-function model by RNAi depletion of GPS2 in human multipotent adipose-derived stem (hMADS) cells. We thoroughly characterized the coregulator depletion-dependent pathway alterations during adipocyte differentiation at the level of transcriptome (RNA-seq), epigenome (ChIP-seq H3K27ac), cistrome (ChIP-seq GPS2), and lipidome. We validated the in vivo relevance of the identified pathways in non-diabetic and diabetic obese patients. The loss of GPS2 triggers the reprogramming of cellular processes related to adipocyte differentiation by increasing the responses to the adipogenic cocktail. In particular, GPS2 depletion increases the expression of BMP4 , an important trigger for the commitment of fibroblast-like progenitors toward the adipogenic lineage and increases the expression of inflammatory and metabolic genes. GPS2-depleted human adipocytes are characterized by hypertrophy, triglyceride and phospholipid accumulation, and sphingomyelin depletion. These changes are likely a consequence of the increased expression of ATP-binding cassette subfamily G member 1 (ABCG1) that mediates sphingomyelin efflux from adipocytes and modulates lipoprotein lipase (LPL) activity. We identify ABCG1 as a direct transcriptional target, as GPS2 depletion leads to coordinated changes of transcription and H3K27 acetylation at promoters and enhancers that are occupied by GPS2 in wild-type adipocytes. We find that in omental adipose tissue of obese humans, GPS2 levels correlate with ABCG1 levels, type 2 diabetic status, and lipid metabolic status, supporting the in vivo relevance of the hMADS cell-derived in vitro data. Our study reveals a dual regulatory role of GPS2 in epigenetically modulating the chromatin landscape and gene expression during human adipocyte differentiation and identifies a hitherto unknown GPS2-ABCG1 pathway potentially linked to adipocyte hypertrophy in humans. • GPS2 depletion in human adipose-derived mesenchymal stem cells increases expression of adipogenic genes, including BMP4. • Loss of GPS2 leads to coordinated changes of epigenome and transcriptome during human adipocyte differentiation. • Loss of GPS2 upregulates ABCG1 and LPL and induces lipidome remodeling including sphingomyelin depletion. • The GPS2-ABCG1 pathway contributes to adipocyte hypertrophy. • GPS2 and ABCG1 levels in omental adipose tissue inversely correlate with type 2 diabetes in obese humans. [ABSTRACT FROM AUTHOR]