ABCA1 and ABCG1 Synergize to Mediate Cholesterol Export to ApoA-I

Gelissen, Ingrid C.; Harris, Matthew J; Rye, Kerry‐Anne; Quinn, Carmel M.; Brown, Andrew; Kockx, Maaike; Cartland, Siân P.; Packianathan, M.; Kritharides, Leonard; Jessup, Wendy

doi:10.1161/01.atv.0000200082.58536.e1

Cited by 374 publications

(319 citation statements)

References 34 publications

(41 reference statements)

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“…ABCG1 has been identified as the more likely mediator of cholesterol transport to HDL but not to lipid poor apoAI [265]. Gelissen et al [266] showed that a range of phospholipids containing acceptors other than HDL subclasses are efficient in mediating the export of cholesterol via ABCG1. Acceptors for ABCG1-mediated cholesterol transport can be generated from incubation of cells with lipid free apoAI through the action of ABCA1 alone.…”

Section: Abcg1mentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

184

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: Abcg1mentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

184

159

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“…HDL formation, or biogenesis, involves the efflux of phospholipids and free cholesterol by ABCA1 to lipid-free apoA-I in the extracellular space, generating nascent HDL particles (27). After ABCA1 facilitates HDL biogenesis, these nascent HDLs become efficient substrates for further lipidation by other cellular pathways (e.g., ABCG1) and esterification of free cholesterol to cholesteryl esters (CEs) by lecithin-cholesterol acyltransferase (LCAT) (28,29). Esterification via LCAT converts the amphipathic cholesterol molecule at the surface of the particle to a nonpolar compound that partitions into the particle's core (28).…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL function

Millar

Duclos

Blesso

2017

Advances in Nutrition

141

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Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their welldocumented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function. Adv Nutr 2017;8:226-39.

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“…Responsive Elements in Their 3′ UTR. Because SREBP-2 and LXR control antagonistic aspects of cellular sterol homeostasis, we hypothesized that miR-33 might be involved in repression of LXR target genes, such as ABCA1 and ABCG1, which are known to promote the efflux of cholesterol from cells (17)(18)(19)(20)(21)(22)(23)(24)(25). Analysis of the 3′ UTR regions of ABCA1 and ABCG1 identified sequences in both genes that are partially complementary to miR-33 sequences (Fig.…”

mentioning

confidence: 99%

miR-33 links SREBP-2 induction to repression of sterol transporters

Marquart

Allen

Ory

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

499

501

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The sterol regulatory element binding protein 2 (SREBP-2) and the liver X receptor (LXR) control antagonistic transcriptional programs that stimulate cellular cholesterol uptake and synthesis, and cholesterol efflux, respectively. The clinical importance of SREBP-2 is revealed in patients with hypercholesterolemia treated with statins, which reduce low-density lipoprotein (LDL) cholesterol levels by increasing hepatic expression of SREBP-2 and its target, the LDL receptor. Here we show that miR-33 is encoded within SREBP-2 and that both mRNAs are coexpressed. We also identify sequences in the 3′ UTR of ABCA1 and ABCG1, sterol transporter genes both previously shown to be regulated by LXR, as targets for miR-33-mediated silencing. Our data show that LXR-dependent cholesterol efflux to both ApoAI and serum is ameliorated by miR-33 overexpression and, conversely, stimulated by miR-33 silencing. Finally, we show that ABCA1 mRNA and protein and plasma HDL levels decline after hepatic overexpression of miR-33, whereas they increase after hepatic miR-33 silencing. These results suggest novel ways to manage hypercholesterolemic patients.

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ABCA1 and ABCG1 Synergize to Mediate Cholesterol Export to ApoA-I

Cited by 374 publications

References 34 publications

Recent advances in physiological lipoprotein metabolism

Recent advances in physiological lipoprotein metabolism

Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL function

miR-33 links SREBP-2 induction to repression of sterol transporters

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