Stimulation of Cholesterol Efflux by LXR Agonists in Cholesterol-Loaded Human Macrophages Is ABCA1-Dependent but ABCG1-Independent

Larrede, Sandra; Quinn, Carmel M.; Jessup, Wendy; Frisdal, Éric; Olivier, Maryline; Hsieh, Victar; Kim, Mi-Jurng; Eck, Miranda Van; Couvert, Philippe; Carrié, Alain; Giral, Philippe; Chapman, M. John; Guérin, Maryse; Goff, Wilfried Le

doi:10.1161/atvbaha.109.194548

Cited by 172 publications

(130 citation statements)

References 27 publications

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“…In contrast, ABCA1 in hepatocytes is essential for nascent HDL formation [298]. In human macrophage foam cells cholesterol efflux stimulated by LXR agonist requires SR-BI and ABCA1 but not ABCG1 [299]. It is likely that the contributions of ABCA1, ABCG1 and SR-BI to cholesterol efflux differ in a tissue-and species-specific manner [300].…”

Section: Scavenger Receptor Bi (Sr-bi)mentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

188

159

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Abstract:Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and posttranscriptional level. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDLcholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several transcription factors, including the liver X receptor and sterol regulatory element binding protein. This review summarizes recent advances in knowledge of the molecular mechanisms regulating lipoprotein metabolism.Keywords: ABCA1; angiopoietin-like proteins; apoC; apoAI; apolipoprotein E (apoE); cholesterol ester transfer protein; chylomicron; LDL receptor; lecithin cholesterol acyl transferase; lipoprotein(a); lipoprotein lipase; microsomal transfer protein; propertin convertase subtilisin/ kexin type 9; SR-BI; phospholipid transfer protein; very low density lipoproteins (VLDL). Abstract 1695

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Section: Scavenger Receptor Bi (Sr-bi)mentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

188

159

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“…Reverse transcription and real-time quantitative PCR using a LightCycler LC480 (Roche) were performed as previously described (13). Expression of mRNA levels was normalized to the human non-POU domain-containing, octamer-binding housekeeping gene (NONO); human a-tubulin (TUBA) and human heat shock protein 90 kDa a (cytosolic); class B member 1 (HSP90AB1) or mouse hypoxanthine phosphoribosyltransferase 1 (Hprt1); mouse non-POU domain-containing, octamer-binding housekeeping gene (Nono); mouse heat shock protein 90 kDa a (cytosolic); class B member 1 (Hsp90ab1); mouse cyclophilin A (CycA); and mouse b-glucuronidase (Gusb) and mouse 18S ribosomal RNA (18S rRNA).…”

Section: Generation Of Stable Abcg1 Knockdown 3t3-l1 Adipocytesmentioning

confidence: 99%

Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity

et al. 2014

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The role of the ATP-binding cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, the ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of lipoprotein lipase (LPL). Because both ABCG1 and LPL are expressed in adipose tissue, we hypothesized that ABCG1 is implicated in adipocyte TG storage and therefore could be a major actor in adipose tissue fat accumulation. Silencing of Abcg1 expression by RNA interference in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during the initial phase of differentiation. Generation of stable Abcg1 knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high-fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 single nucleotide polymorphisms (rs1893590 [A/C] and rs1378577 [T/G]) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with increased PPARγ expression and adiposity concomitant to increased fat mass and BMI (haplotype AT>GC). The critical role of ABCG1 in obesity was further confirmed in independent populations of severe obese and diabetic obese individuals. This study identifies for the first time a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity.

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“…However, the relative contribution of the ABCA1, scavenger receptor class B type I (SR-BI)/Cla1, and ABCG1 pathways to cholesterol export from macrophages is species specifi c ( 18 ). In human macrophages, ABCA1 is considered to be the major cholesterol transporter which interacts preferentially with lipid-poor ApoAI ( 19,20 ).…”

Section: Fc Effl Ux Assaysmentioning

confidence: 99%

“…Of secondary importance, the SR-BI/Cla-1 receptor promotes bidirectional cholesterol fl uxes and interacts mostly with large HDL particles in order to facilitate the exit of free cholesterol (FC) from macrophages ( 21 ). The ABCG1 transporter plays an important role in cholesterol effl ux from mouse macrophages, however its contribution to promoting cholesterol effl ux from human macrophages is mostly insignifi cant ( 18,22 ).To date, no study has investigated the effect of HIV infection or its treatment on the ability of HDL particles to stimulate cholesterol effl ux from human macrophages. We hypothesize that HIV infection might induce the appearance of dysfunctional HDL particles, thus reducing cholesterol effl ux from human macrophages and favoring atherosclerosis progression.…”

Section: Fc Effl Ux Assaysmentioning

confidence: 99%

Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV-infected patients: impact of HAART

Khoury

Ghislain

Villard

et al. 2015

Journal of Lipid Research

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Coronary heart disease rates are expected to be higher as the human immunodefi ciency virus (HIV) population ages. Controversy still exists as to whether HIV infection per se or its treatment increases the rate of coronary heart disease. Highly active antiretroviral therapy (HAART) has been associated with the occurrence of cardiovascular events in HIV-infected patients ( 1, 2 ). However, in the Strategies for Managment of Antiretroviral Therapy (SMART) trial, the episodic use of HAART was associated with an increased risk of CVD when compared with continuous HAART use ( 3 ). It is now well-established that atherosclerosis Abstract The capacity of HDL to remove cholesterol from macrophages is inversely associated with the severity of angiographic coronary artery disease . The effect of human immunodefi ciency virus (HIV) infection or its treatment on the ability of HDL particles to stimulate cholesterol effl ux from human macrophages has never been studied. We evaluated the capacity of whole plasma and isolated HDL particles from HIV-infected subjects (n = 231) and uninfected controls (n = 200), as well as in a subset of 41 HIV subjects receiving highly active antiretroviral therapy (HAART) to mediate cholesterol effl ux from human macrophages. Plasma cholesterol effl ux capacity was reduced ( ؊ 12%; P = 0.001) in HIV patients as compared with controls. HIV infection reduced by 27% ( P < 0.05) the capacity of HDL subfractions to promote cholesterol effl ux from macrophages. We observed a reduced ABCA1-dependent effl ux capacity of plasma ( ؊ 27%; P < 0.0001) from HIV-infected subjects as a result of a reduction in the effl ux capacity of HDL3 particles. HAART administration restored the capacity of plasma from HIV patients to stimulate cholesterol effl ux from human macrophages (9.4%; P = 0.04). During HIV infection, the capacity of whole plasma to remove cholesterol from macrophages is reduced, thus potentially contributing to the increased coronary heart disease in the HIV population. HAART administration restored the removal of cholesterol from macrophages by increasing HDL functionality. -El Khoury, P., M. Ghislain,

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Stimulation of Cholesterol Efflux by LXR Agonists in Cholesterol-Loaded Human Macrophages Is ABCA1-Dependent but ABCG1-Independent

Cited by 172 publications

References 27 publications

Recent advances in physiological lipoprotein metabolism

Recent advances in physiological lipoprotein metabolism

Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity

Plasma cholesterol efflux capacity from human THP-1 macrophages is reduced in HIV-infected patients: impact of HAART

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