Article Figures & Data
Figures
- Fig. 1.
Cholesterol uptake, distribution, and peripheral utilization. (I) Schematic overview illustrating intestinal cholesterol (light yellow spheres) uptake by enterocytes, including cholesterol esterification and apoB-48 binding, which facilitates cholesterol efflux to the lymphatic system. (II) The resulting nascent chylomicrons are subsequently transported to the blood, where they collide with HDL particles that transfer apoE and apoC-II to chylomicrons, leading to their maturation. (III) Mature chylomicrons can be converted to chylomicron remnants by endothelial lipoprotein lipase (LPL) activated by apoC-II, which releases free fatty acids (yellow spheres) for uptake in peripheral tissues (e.g., muscles and fat) and apoC-II for translocation to HDL. (IV) Next, chylomicron remnants are imported into hepatocytes via the chylomicron remnant receptor (CRR), which releases the remaining cholesterol and apoE by lysosomal degradation. The resulting hepatic free cholesterol, which may also originate from de novo synthesis, can be exported as VLDL particles upon binding to apoB-100. (III) Removal of triglycerides by endothelial LPL converts VLDL particles into intermediate density lipoprotein (IDL) particles. They can collide with HDL to acquire apoE. (IV) Hepatic lipase (HL) subsequently hydrolyzes the remaining triglycerides in IDL, which forms LDL particles (III) that can also be formed by LPL (III) out of IDL particles, and that are able to release cholesterol to peripheral tissues via LDLR.
- Fig. 2.
Reverse cholesterol transport. Schematic overview of reverse cholesterol transport, (I) which is initiated by the efflux of cholesterol (yellow spheres) by ABCA1 and ABCG1 transporters. They are expressed on a variety of peripheral tissues, including macrophages that engulf cholesterol from atherosclerotic plaques (i.e., foam cells). ABCA1-mediated cholesterol efflux transfers cholesterol to lipid-poor apoA-I, leading to the formation of pre-βHDL. These particles can be converted by circulating lecithin:cholesterol acyltransferase (LCAT) into HDL particles, which function as cholesterol acceptor for ABCG1. Cholesterol efflux by ABCG1 is mediated via reorganization of cholesterol in the plasma membrane, which increases plasma membrane cholesterol concentrations. Subsequently, aqueous diffusion could increase the cholesterol efflux out of the cell to HDL without necessity of HDL to bind to the plasma membrane. (II) SR-BI mediates cholesterol influx into hepatocytes without whole HDL particle uptake, allowing unbound apoA-I to circulate and enter a new RCT cycle. Finally, hepatic free cholesterol can be directly removed to bile canaliculi by ABCG5 and ABCG8 transporters, or indirect via conversion by cytochrome P450 (CYP)7A1 into bile acids (green spheres) that can subsequently be transported into bile via the multidrug resistance protein (MRP)2/ABCC2 and bile salt export pump (BSEP/ABCB11) transporters, located on the canalicular membrane.
- Fig. 3.
Flow chart of systematic literature search strategy. Overview of the number of publications retrieved from all MEDLINE and EMBASE searches and exclusion criteria applied to these publications, including removal of duplicates and title- and abstract-based screenings conducted by two independent reviewers. For a detailed overview of the search strategies, see Supplemental Tables 1 and 2.
- Fig. 4.
Potential ABCA1- and ABCG1-driven cholesterol efflux modes. ABCA1-driven cholesterol efflux to lipid-poor apoA-I is hypothesized to occur either at the plasma membrane (upper left panel), or via endocytosis of the apoA-I–bound ABCA1 transporter, followed by intracellular lipid loading and exocytosis (upper right panel). ABCA1 is ubiquitously expressed, particularly at high levels in liver, small intestine, macrophages, adrenal glands, lungs, placenta, and fetal tissue. The transporter initiates cellular cholesterol efflux to the lymph and bloodstream via a specific interaction with apoA-I. Six different mechanisms have been proposed for the interaction between apoA-I and ABCA1 (small boxes), including the following: outward translocation of phosphatidylserine (PS) by ABCA1 floppase activity allowing apoA-I binding; direct binding of apoA-I to extracellular ABCA1 loop domains; ABCA1 floppase activity leading to the formation of protrusions facilitating apoA-I binding; ABCA1 floppase activity leading to the outward translocation of phosphatidylinositol 4,5-bisphosphate (PIP2), allowing apoA-I to bind and unfold, followed by microsolubilization of the membrane; low-affinity binding to ABCA1 and high-affinity binding to cholesterol; dimerization of ABCA1 transporter proteins is initiated by loading of the extracellular loop domains with cholesterol, followed by apoA-I binding to the dimerized cholesterol-loaded extracellular loop domains (ED). ABCG1-driven cholesterol efflux to HDL particles in the bloodstream or lymph is expected to be the result of a collision of these particles with cholesterol molecules that protrude from the plasma membrane (lower left panel), mediated either by a direct effect of the ABCG1 dimer on the membrane structure or by outward translocation via ABCG1 floppase activity (lower right panel). ABCG1 is expressed in many cell types, including macrophages, neurons, astrocytes, endothelial and epithelial cells, and many tissues (e.g., liver, intestine, kidney, spleen, lung, and brain), where it mediates basolateral cholesterol efflux.
- Fig. 5.
Cellular regulation of ABCA1 and ABCG1 transporter expression. Expression of ABCA1 and ABCG1 transporters is increased by stimulation of the nuclear PPAR, which upon dimerization with RXR (i.e., another nuclear factor) bind to the PPAR-responsive element (PPRE), leading to the transcription of the nuclear LXR and RAR, respectively (right upper panel). Next, dimerization of LXR or RAR with RXR enables binding to the LXRE, inducing the transcription of ABCA1 and ABCG1, respectively. Once transcribed, the stability of ABCA1 and ABCG1 mRNA can either be enhanced or decreased upon binding of miRNAs, of which an overview is provided in Table 4 (right middle panel). ABCA1 and ABCG1 plasma membrane expression is also mediated via modulation of its lysosomal (blue vesicle) or endosomal (orange vesicle) degradation. The latter is stimulated by phosphorylation of the PEST sequence by apelin-13 (AP-13) via PKCα (left lower panel). Upon phosphorylation, calpain (CALP) can bind and initiate proteolysis, a process that is stimulated by calpastatin (CPSTAT), and negatively affected by calmodulin (CM) or by the HO-1 axis. Finally, the ability of ABCA1 and ABCG1 to bind lipid poor apoA-I is stimulated upon transporter phosphorylation by PKA at Ser-1042 and Ser-2054, located in the nucleotide binding domain of ABCA1. PKA is positively regulated by cAMP levels that depend on the balance of cAMP breakdown by PDE, formation by adenosine receptor–stimulated AC, and efflux by multidrug resistance protein (MRP) 4 and 5 (right lower panel).
Tables
- TABLE 1
LXR-activating compounds
Overview of compounds that activate LXR, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference Acetyl-podocarpic dimer Selective LXR agonist ↑ THP-1 ↑ Caco-2 THP-1 Sparrow et al., 2002 ↑ Caco-2 ↑ Primary hepatocytesa ↑ apoA-I ↑ Primary hepatocytesa ↑ Caco-2 ↑ Monocytesa Primary fibroblastsa: ↑ apoA-I Baclofen GABAB receptor agonist — — MDM Yang et al., 2014 = apoA-I = HDL Digoxin Na+-K+-ATPase inhibitor ↑ H9c2 — ↑ H9c2 Campia et al., 2012 Disodium ascorbyl phytostanol phosphate (FM-VP4) MDR1 antagonist ↑ Liverb — — Méndez-González et al., 2010 = Small intestineb Daunorubicin Anthracycline antibiotic = HL-1 = HL-1 — Monzel et al., 2017 DMHCA LXRα agonist ↑ THP-1 ↑ BREC ↑ THP-1 Quinet et al., 2004; Kratzer et al., 2009; Hammer et al., 2017 ↑ J774 ↑ PMc ↑ HepG2 ↑ Livera,d ↑↑ BREC ↑ Ileumd ↑ PMb,c ↑ Aortad ↑ Livera = Liverd ↑ Ileumd ↑ Aortad Doxorubicin Anthracycline antibiotic ↑ HL-1 ↑ HL-1 HL-1 Monzel et al., 2017 ↑ apoA-I ↑ HDL E17110 Benzofuran-2-carboxylate analog ↑↑ RAW264.7 ↑↑ RAW264.7 RAW264.7 Li et al., 2016 ↑ apoA-I ↑ HDL (E)-1-(e,4-diisopropoxyphenyl)-3-(4-isopropoxy-3-methoxyphenyl-2-en-1-one Chalcone derivative ↑↑ THP-1 ↑ THP-1 — Teng et al., 2018 Ergosterol derivatives Ergosterol analog ↑ U937 Marinozzi et al., 2017 Etoposide DNA topoisomerase II inhibitor ↑ RAW264.7 ↑ PMb ↑ PM Zhang et al., 2013a ↑↑ PMb ↑ RCTb ↑ THP-1 Blood monocytea EXEL-04286651/BMS-779788 LXR partial agonist ↑ Murine blood cells ↑ Murine blood cells — Kick et al., 2015; Kirchgessner et al., 2015 ↑ Blood cellse FTY720-P Sphingosine-1-phosphate analog ↑ Monocytesa — ↑ Monocytesa Blom et al., 2010 G004 Unknown (synthetic sulfonylurea compound) ↑↑ RAW264.7 ↑↑ RAW264.7 ↑ RAW264.7 Qian et al., 2017 ↑ Liverc ↑↑ Liverc ↑ RCTc GW3965 LXRα agonist ↑ THP-1 ↑ haSMCa ↑ THP-1 Miao et al., 2004; Quinet et al., 2004, 2006; Brunham et al., 2006; Naik et al., 2006; Delvecchio et al., 2007; DiBlasio-Smith et al., 2008; Kannisto et al., 2014 ↑ J774 ↑= Liverb ↑ RCTb ↑ HepG2 ↑ Peripheral bloodf ↑ haSMCa ↑ Spleenf ↑ BMM ↑ Prox small intestineb,g ↑ PMb,h,i ↑↑ Livera,h ↑= Livera,h ↑ Peripheral bloodf ↑ Spleenf ↑↑ Prox small intestineb = Prox small intestineg ↑ Kidneyb,h ↑ Duodenumb,h Ibandronate Osteoclast inhibitor ↑ MM6 — ↑ MM6 Strobach and Lorenz, 2003 ↑ PBMCsa Ibrolipim (NO-1886) Lipoprotein lipase activator ↑↑ THP-1 ↑↑ THP-1 ↑ THP-1 Zhang et al., 2006; Ma et al., 2009; Chen et al., 2010 ↑↑ Liverj ↑↑ Adipose tissuej ↑↑ Aortaj Idarubicin Anthracycline antibiotic ↑ HL-1 ↑ HL-1 Monzel et al., 2017 IMB-151 Unknown ↑↑ RAW264.7 ↑↑ RAW264.7 ↑ RAW264.7 Li et al., 2014 Infliximab Anti–TNF-α mAb ↑↑ THP-1 == THP-1 ↑ THP-1 (restores effect of TNF-α) Voloshyna et al., 2014 Lansoprazole Proton pump inhibitor ↑ H4 neuroglioma cellsa — — Cronican et al., 2010 ↑ U-87 astrocytoma ↑↑ CCF astrocytoma ↑ U-118 astrocytoma ↑ Primary astrocytesb LXR-623 Synthetic LXR agonist ↑ Duodenumg ↑ Duodenumg — DiBlasio-Smith et al., 2008; Katz et al., 2009; Quinet et al., 2009 = Liverg = Liverg ↑ Spleenf ↑ Spleenf ↑ Peripheral blooda,b,f ↑ Peripheral blooda,b,f ↑↑ PBMCsa ↑↑ PBMCsa ↑ Whole blooda,e ↑ Whole blooda,e Methyl-3β-hydroxy-5α,6α-epoxycholanate LXRα agonist ↑ THP-1 — — Yan et al., 2010 ↑ Aortac Omeprazole Proton pump inhibitor ↑ H4 neuroglioma cellsa — — Cronican et al., 2010 Pantoprazole Proton pump inhibitor ↑ H4 neuroglioma cella — — Cronican et al., 2010 Ouabain Na+-K+-ATPase inhibitor ↑ H9c2 — ↑ H9c2 Campia et al., 2012 Ritonavir Viral proteinase inhibitor ↑↑ THP-1 = THP-1 — Pou et al., 2008 Sirolimus FK-binding protein-12 inhibitor ↑ hVSMC = hVSMC = hVSMC Ma et al., 2007 (24S)-stigmasta-5,28-diene-3β,24- ol LXR agonist ↑ U937 Castro Navas et al., 2018 (24S)-stigmasta-5-ene-3β,24-ol LXR agonist ↑ U937 Castro Navas et al., 2018 Stigmasterol derivatives LXR agonist ↑ U937 Marinozzi et al., 2017 T0901317 LXR agonist ↑↑ THP-1 ↑ THP-1 ↑ THP-1 Fukumoto et al., 2002; Murthy et al., 2002; Terasaka et al., 2003; Thomas et al., 2003; Beyer et al., 2004; Miao et al., 2004; Quinet et al., 2004, 2006; Wu et al., 2004; Panzenboeck et al., 2006; Wang et al., 2006; Delvecchio et al., 2007, 2008; Fujiyoshi et al., 2007; Sprecher et al., 2007; Dai et al., 2008; DiBlasio-Sato et al., 2008; Smith et al., 2008; Zanotti et al., 2008; Larrede et al., 2009; Verschuren et al., 2009; Mogilenko et al., 2010; Morrow et al., 2010; Yan et al., 2010; Maejima et al., 2011; Honzumi et al., 2011; Chen et al., 2012; Di et al., 2012; El Roz et al., 2012; Elali and Hermann, 2012; Jiang et al., 2012; Ma et al., 2014; Kaneko et al., 2015; Kirchgessner et al., 2015; Manna et al., 2015; Tamehiro et al., 2015; Li et al., 2016; Carter et al., 2017; Jiang and Li, 2017; Marinozzi et al., 2017; Monzel et al., 2017; Kaseda et al., 2018 ↑↑ RAW264.7 ↑↑ RAW264.7 ↑ HDL ↑ J774 ↑ MCF-7 ↑ J774 ↑ U937 ↑↑ Caco-1 ↑ Caco-1 ↑↑ HepG2 ↑ HL-1 HL-1 ↑↑ Caco-1 ↑ TR-CSFB3 ↑ apoA-I ↑ HL-1 ↑↑ haSMCa ↑ HDL ↑↑ pBCECs ↑ Cerebral endothelial cells ↑ SAS ↑ TR-CSFB3 ↑↑ Blood-derived macrophagesa ↑ Jurkat ↑↑ SAS ↑ Aorta endothelial cellsc ↑ Fu5AH ↑↑ haSMC ↑ Liverb,k ↑ COS-7 ↑↑ McARH7777 ↑ Aortai,o ↑ pBCECs ↑↑ CD4+ T cellsa ↑ Peripheral bloode,f ↑ Monocyte-derived macrophagesa ↑↑ Jurkat ↑ CD4+ T cellsa ↑ Cerebral endothelial cells ↑ HSKMca ↑ Murine immortal macrop. haSMCa ↑ Murine neuro2A = apoA-I ↑ Murine BV-2 ↑ HDL ↑ Rat C6 MCF-7 ↑↑ Blood-derived macropg = apoA-I ↑ Aorta endothelial cellsc ↑ HDL ↑ Renal glomerular mesangial cellsi ↑ Murine primary macrop. ↑↑ PMb,d,g,h ↑ PMb,d,g,h ↑↑ Liver b,c,h,i,l,k ↑ Murine immortal macrop. ↑↑ Aortab,c,i,k,o ↑ Renal glomerular mesangial cellsi ↑ Small intestinec ↑ Kidneyb,h ↑ Duodenumb,h ↑ Peripheral bloodf ↑ Proximal intestinek ↑ Distal intestinek ↑↑ Brainm,n Tacrolimus FK-binding protein-12 inhibitor ↑= THP-1 — — Jin et al., 2004 Teniposide DNA topoisomerase II inhibitor ↑ RAW264.7 ↑ PMb ↑ PMb Zhang et al., 2013a ↑↑ PMb ↑ RCT ↑ THP-1 ↑ Blood monocyte Topiramate GABA-A receptor agonist ↑↑ MDM ↑↑ MDM MDM Yang et al., 2014 ↑ apoA-I ↑ HDL YC-1 Soluble guanylyl cyclase activator ↑↑ J774A.1 = J774A.1 ↑ J774A.1 Tsou et al., 2014 ↑ Aortac = Aortac BMM, bone marrow– derived macrophage; BREC, bovine retinal endothelial cells; haSMC, human airway smooth muscle cells; HSKM, human skeletal muscle cells; hVSMC, human vascular smooth muscle cells; macrop, macrophage; MCF-7, Michigan Cancer Foundation-7; MDM, monocyte-derived macrophage; pBCECs, procine brain capillary endothelial cells; PBMC, peripheral blood mononuclear cell; PM, peritoneal macrophages; prox, proximal; SAS, human squamous cell carcinoma cell line.
↵a Human.
↵b C75BL/6 mice.
↵c apoE−/− C57BL/6 mice.
↵d LXRβ−/− C75BL/6 mice.
↵e Cynomolgus monkeys.
↵f Male long Evans rats.
↵g LDLR−/− C75BL/6 mice.
↵h LXRα−/− C75BL/6 mice.
↵i New Zealand White rabbits.
↵j Male chine Bama minipigs.
↵k Male SD rats.
↵l 129Sv mice.
↵m APP/PS1∆9/APOE4+/+/ABCA1+/− C57 BL/6 mice.
↵n APP/PS1∆9/APOE3+/+/ABCA1+/− C57 BL/6 mice.
↵o E3L mice.
- TABLE 2
PPAR-activating compounds
Overview of compounds that activate PPARs, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference PPARγ-activating compounds 15d-PGJ2 Prostanoid-specific receptor inhibitor ↑ THP-1 ↑ PMa Lipid-loaded HMC Ruan et al., 2003; Jiang and Li, 2017 ↑ HMC ↑ apoA-I ↓↓ PMa PMa ↓ apoA-I ↑ HDL 4010B-30 Benzamide analog ↑ RAW264.7 — RAW264.7 Du et al., 2015b ↑ HepG2 ↑ apoA-I Ciglitazone PPARγ agonist ↑= THP-1 ↑ THP-1 ↑ THP-1 Argmann et al., 2003, 2005 E3317 PPARγ agonist RAW264.7 RAW264.7 Wang et al., 2018 ↑↑ LO2 ↑ apoA-I GQ-11 PPARγ/α agonist ↑ Liverb Silva et al., 2018 GW1929 PPARγ agonist ↑↑ HepG2 — — Mogilenko et al., 2010 GW7845 PPARγ agonist ↑ THP-1 — ↑ THP-1 Chawla et al., 2001; Oliver et al., 2001 Propofol GABAB receptor agonist ↑↑ THP-1 ↑↑ THP-1 ↑ THP-1 Ma et al., 2015; Hsu et al., 2018 ↑ RAECs RAECs ↑ HDL Lysophosphatidylcholine Unknown ↑↑ PMa — ↑ PMa Hou et al., 2007 Mycophenolic acid Inosine-5′-monophosphate dehydrogenase inhibitor ↑↑ HepG2 — — Xu et al., 2011 Pioglitazone PPARγ agonist ↑↑ THP-1 ↑↑ THP-1 THP-1 Panzenboeck et al., 2006; Nakaya et al., 2007; Tanabe et al., 2008; Ogata et al., 2009; Cocks et al., 2010; Ozasa et al., 2011; Wang et al., 2014b, 2015b; Jiang and Li, 2017; Silva et al., 2018 ↑ HepG2 ↑ Monocyte-derived macrop ↑ apoA-I ↑↑ pBCECs ↑ PMa ↑ HDL ↑ gBECs ↑ Diabetic patientsc ↓ pBCECs ↑↑ WI38 fibroblasts ↑ Rat cortical neurons ↑ gBECs ↑ Monocyte-derived macropc ↑ WI38 fibroblasts ↓↓ PMa PMa = Liverb ↓ apoA-I ↑ Diabetic patientsc ↑ HDL ↑ Rat cortical neurons ↑ Diabetic patientsc Rosiglitazone PPARγ agonist ↑↑ THP-1 ↑↑ THP-1 ↑ THP Chawla et al., 2001; Chinetti et al., 2001; Claudel et al., 2001; Li et al., 2004, 2015; Llaverias et al., 2006 ↑ RAW264.7 ↑ macropd ↑ RAW264.7 ↑ HepG2 ↑ Aortad ↑ macropd == macropd ↑ PMe ↑ PMe ↑ Hepatocytese ↑= Hepatocytese = Aortad Aorta lesione Telmisartan Angiotensin receptor 1 antagonist ↑↑ THP-1 ↑↑ THP-1 ↑ THP-1 Nakaya et al., 2007 ↑ Monocyte-derived macropc ↑ Monocyte-derived macropc Troglitazone PPARγ agonist ↑ THP-1 ↑ PMa ↑ pBCECs Cabrero et al., 2003; Panzenboeck et al., 2006; Lee et al., 2008; Jiang and Li, 2017 ↓↑ pBCECs PMa ↑↑ gBECs ↓ apoA-I = Monocyte-derived macropc ↑ HDL ↓↓ PMa PPARα-activating compounds Aspirin COX-1/2 inhibitor ↑ THP-1 — RAW264.7 Viñals et al., 2005; Wang et al., 2010 ↑↑ RAW264.7 ↑ apoA-I Atorvastatin HMG-CoA reductase inhibitor ↑ THP-1 ↑ THP-1 THP-1 Argmann et al., 2005; Maejima et al., 2011; Nicholls et al., 2015, 2017 ↑ McARH7777 ↑ apoA-I ↑ HDL Bezafibrate Pan-PPAR agonist ↑↑ THP-1 — ↑ THP-1 Cabrero et al., 2003; Ruan et al., 2003; Panzenboeck et al., 2006; Hossain et al., 2008; Inaba et al., 2008; Ogata et al., 2009 ↑↑ HepG2 ↑ HepG2 == pBCECs = pBCECs ↑↑ W138 fibroblast ↑ W138 fibroblast ↑ HMC Lipid-loaded HMC ↑↑ Primary hepatocytes ↑ apoA-I = Monocyte-derived macropc ↑ Primary hepatocytes = aortab Clofibrate PPARα agonist ↑= HepG2 — — Guan et al., 2003; Kobayashi et al., 2011 = Primary hepatocytesf ↑ Liverf Fenofibrate PPARα agonist ↑↑ THP-1 ↑ Liverg ↑ THP-1 Forcheron et al., 2002; Lin and Bornfeldt, 2002; Cabrero et al., 2003; Thomas et al., 2003; Arakawa et al., 2005; Kooistra et al., 2006; Hossain et al., 2008; Tanabe et al., 2008; Ogata et al., 2009; Jiang and Li, 2017 ↑↑ RAW264.7 ↑ RAW264.7 ↑↑ HepG2 ↑ HepG2 =↑ pBCECs = pBCECs ↑↑ Balb/3T3 = Balb/3T3 ↑↑ W138 fibroblast ↑ W138 fibroblast ↑↑ Primary hepatocytes ↑ Primary hepatocytes = Monocyte-derived macropc ↑ PMa ↑ Liverh ↑ Diabetic patientsc ↑ Aortai Gemfibrozil PPARα agonist ↑↑ THP-1 — ↑ THP-1 Hossain et al., 2008; Ogata et al., 2009 ↑↑ HepG2 ↑ HepG2 ↑↑ W138 fibroblast ↑ W138 fibroblast ↑↑ Primary hepatocytes ↑ Primary hepatocytes GW7647 PPARα agonist ↑ THP-1 = macropd = THP-1 Oliver et al., 2001; Li et al., 2004; Wang et al., 2010; Nakaya et al., 2011 ↑↑ RAW264.7 = Aortad RAW264.7 == macropd ↑↑ BMMa ↑ apoA-I == Atherosclerotic lesiond = macropd ↑↑ BMMa ↑ BMMa LY518674 PPARα agonist ↑↑ THP-1 — ↑ THP-1 Hossain et al., 2008; Ogata et al., 2009 ↑↑ HepG2 ↑ HepG2 ↑↑ W138 fibroblast ↑ W138 fibroblast ↑↑ Primary hepatocytes ↑ Primary hepatocytes Pitavastatin HMG-CoA reductase inhibitor ↓ J774 — ↓ J774 Zanotti et al., 2004, 2006; Kobayashi et al., 2011; Maejima et al., 2011 ↑ HepG2 ↑ Fu5AH ↑↑ McARH7777 ↓ PMa,b,d ↑ Liverf = LXR−/− mice Pravastatin HMG-CoA reductase inhibitor ↑↑ 3T3-L1 ↓↓ 3T3-L1 ↓ 3T3-L1 Maejima et al., 2011; Mostafa et al., 2016 = McARH7777 Rosuvastatin HMG-CoA reductase inhibitor = Hepatocytesa ↑ J774 Shimizu et al., 2014; Mostafa et al., 2016 ↑ BMMa ↑ RCTa Simvastatin HMG-CoA reductase inhibitor ↑ McARH7777 == PMi THP-1 Argmann et al., 2005; Guan et al., 2008; Maejima et al., 2011; Song et al., 2011; Ying et al., 2013; Gong et al., 2014 ↑ Diabetic patients with hyperlipidemia == Liveri ↑ apoA-I == PMd = HDL ↑↑ Liveri ↑ RAW264.7 WY14643 PPARα agonist ↑↑ THP-1 ↑ THP-1 ↑ THP-1 Chinetti et al., 2001; Ruan et al., 2003; Beyer et al., 2004; Arakawa et al., 2005; Lee et al., 2008; Maejima et al., 2011 ↑↑ RAW264.7 ↑ RAW264.7 ↑↑ gBECs = Balb/3T3 ↑↑ Balb/3T3 Lipid-loaded HMC = McARH7777 ↑ apoA-I ↑ Livera Wy,14,563 PPARα agonist — — ↑ THP-1 Chawla et al., 2001 PPARδ/β-activating compounds Carbaprostacyclin (cPGI) PPARδ agonist — — ↑ THP-1 Chawla et al., 2001 GW0742 PPARδ agonist = Livera = Livera ↑ BMMa Li et al., 2004; Briand et al., 2009 = Small intestinea = Small intestinea = macropa == macropd = macropd = Atherosclerotic lesiond = Aortad GW501515 PPARδ agonist ↑↑ THP-1 = HSKM ↑ THP-1 Oliver et al., 2001; Sprecher et al., 2007; Ogata et al., 2009 ↑↑ W138 fibroblast ↑ W138 fibroblast ↑ 1BR3N fibroblast ↑ 1BR3N fibroblast ↑ Intestinal FHS74 ↑ Intestinal ↑ HSKM HSKM BMM, bone marrow– derived macrophage; gBECS, gallbladder epithelial cells; HMC, human mast cell; HSKM, human skeletal muscle cell; macrop, macrophage; pBCECs, porcine brain capillary endothelial cells; PM, peritoneal macrophages; RAECs, rat aortic endothelial cells.
↵a C75BL/6 mice.
↵b LDLR−/− C75BL/6 mice.
↵c Human.
↵d LDLR−/− C75BL/6 hypercholesterolemic mice.
↵e New Zealand White rabbits.
↵f Male Wistar rats.
↵g Male Zucker diabetic fatty rats.
↵h 129SV mice.
↵i Female E3L transgenic mice.
- TABLE 3
Synthetic retinoid nuclear receptor agonists
Overview of retinoid nuclear receptor agonists, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference RXR agonists Bexarotene pan-RXR agonist ↑↑ BLECs — ↑ BLECs LaClair et al., 2013; Kuntz et al., 2015; Tachibana et al., 2016 ↑ Cortexa ↑ Cortexb ↑ Cortexc HX630 RXR agonist ↑ THP-1 ↑ THP-1 ↑ THP-1 Nishimaki-Mogami et al., 2008 ↑ RAW264.7 LG101305 RXR agonist ↑ RAW264.7 — ↑ RAW264.7 Claudel et al., 2001 LG268 RXR agonist ↑ Small intestined — ↑ THP-1 Chawla et al., 2001 ↑ PM Methoprene RXR agonist ↑ Astrocyte ↑ Astrocyte Astrocyte Repa et al., 2000; Chen et al., 2011b ↑ apoA-I ↑ HDL PA024 RXR agonist ↑ THP-1 ↑ THP-1 ↑ THP-1 Nishimaki-Mogami et al., 2008 ↑ RAW264.7 Tri-butylin chloride RXRα agonist ↑↑ RAW264.7 ↑↑ Primary mouse astrocyte cells ↑ RAW264.7 Cui et al., 2011; Sun et al., 2015 ↑↑ Primary mouse astrocyte cells ↑↑ Cortexc ↑↑ Cortexc RAR agonists AM580 RARα agonist — ↑ THP-1 — Ayaori et al., 2012 TTNPB Synthetic RAR agonist ↑ THP-1 ↑ THP-1 ↑ RAW264.7 Costet et al., 2003; Chen et al., 2011b; Ayaori et al., 2012 ↑ HEK293 ↓ Astrocytes ↓ Astrocytes ↓ Astrocytes = Liverd = Liverd ↑ PMd - TABLE 4
Overview of microRNAs enhancing or reducing ABCA1 and ABCG1 mRNA
Overview of microRNAs, including their effects on ABCA1 and ABCG1 expression. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased.
MicroRNA ABCA1 ABCG1 Reference miR-10b ↓ ↓ Hazen and Smith, 2012; Wang et al., 2012; Dávalos and Fernandez-Hernando, 2013; Goedeke et al., 2014; Rayner and Moore, 2014; Rotllan et al., 2016; Aryal et al., 2017 miR-17 ↓ He et al., 2015 miR-19b ↓ Lv et al., 2014, 2015; DiMarco and Fernandez, 2015 miR-20a/b ↓ Liang et al., 2017 miR-21 ↓ ↓ Canfrán-Duque et al., 2017 miR-26 ↓ ↓ (Indirect via LXR) Sun et al., 2012; Dávalos and Fernandez-Hernando, 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014; Rayner and Moore, 2014; DiMarco and Fernandez, 2015; Yang et al., 2015; Feinberg and Moore, 2016; Rotllan et al., 2016 miR-27a/b ↓ = (↓ Indirect) Kang et al., 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014, 2015b; Zhang et al., 2014; DiMarco and Fernandez, 2015; Yang et al., 2015; Rotllan et al., 2016 miR-33a/33b ↓ ↓ Moore et al., 2010, 2011; Fernandez-Hernando et al., 2011; Fernández-Hernando and Moore, 2011; Rayner et al., 2011, 2012; Iatan et al., 2012; Rotllan and Fernandez-Hernando, 2012; Dávalos and Fernandez-Hernando, 2013; Kang et al., 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014; Mao et al., 2014; Rayner and Moore, 2014; DiMarco and Fernandez, 2015; He et al., 2015; Mandolini et al., 2015; Yang et al., 2015; Feinberg and Moore, 2016; Ono, 2016; Rotllan et al., 2016; Aryal et al., 2017 miR-93 ↓ He et al., 2015 miR-96 ↓ Moazzeni et al., 2017 miR-101 ↓ Zhang et al., 2015a; Aryal et al., 2017 miR-106b ↓ Kim et al., 2012; Rotllan and Fernandez-Hernando, 2012; Dávalos and Fernandez-Hernando, 2013; Goedeke et al., 2014; Rayner and Moore, 2014; Feinberg and Moore, 2016 miR-128-1 ↓ Wagschal et al., 2015; Feinberg and Moore, 2016; Rotllan et al., 2016; Aryal et al., 2017 miR-128-2 ↓ ↓ Adlakha et al., 2013; DiMarco and Fernandez, 2015 miR-130b ↓ Wagschal et al., 2015; Feinberg and Moore, 2016 miR-144 ↓ ↓ (Indirect via RXR) de Aguiar Vallim et al., 2013; Kang et al., 2013; Ramírez et al., 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014; Rayner and Moore, 2014; DiMarco and Fernandez, 2015; Feinberg and Moore, 2016; Rotllan et al., 2016; Aryal et al., 2017 miR-145 ↓ Kang et al., 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014; Sala et al., 2014; DiMarco and Fernandez, 2015 miR-148a ↓ Kang et al., 2013; Goedeke et al., 2015a; Wagschal et al., 2015; Feinberg and Moore, 2016; Rotllan et al., 2016; Aryal et al., 2017 miR-223 ↑ DiMarco and Fernandez, 2015; Rotllan et al., 2016 miR-301b ↓ Wagschal et al., 2015; Feinberg and Moore, 2016 miR-302a ↓ DiMarco and Fernandez, 2015; Meiler et al., 2015; Rotllan et al., 2016; Aryal et al., 2017 miR-378 ↓ (Indirect) Wang et al., 2014a; DiMarco and Fernandez, 2015; Yang et al., 2015 miR-613 ↓ Zhao et al., 2014; DiMarco and Fernandez, 2015 miR-758 ↓ Ramirez et al., 2011; Kim et al., 2012; Rayner et al., 2012; Rotllan and Fernandez-Hernando, 2012; Dávalos and Fernandez-Hernando, 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014; Rayner and Moore, 2014; DiMarco and Fernandez, 2015; Mandolini et al., 2015; Yang et al., 2015; Feinberg and Moore, 2016 miR, microRNA.
- TABLE 5
Compounds enhancing ABCA1 and ABCG1 mRNA stability
Overview of compounds that enhance ABCA1 and ABCG1 mRNA stability, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference AICAR AMPK agonist == J774.A1 ↑↑ J774.A1 J774.A1 Li et al., 2010; Kemmerer et al., 2016 ↑ THP-1 ↑↑ PMa ↑ HDL A769662 Allosteric AMPK agonist ↑↑ THP-1 ↑ J774.A1 ↑ THP-1 Li et al., 2010; Kemmerer et al., 2016 Salicylate Allosteric AMPK agonist ↑ THP-1 — — Kemmerer et al., 2016 ↵a apoE−/− C75BL/6 mice.
PM, peritoneal macrophages.
- TABLE 6
Inhibitors of ABCA1 and ABCG1 protein breakdown
Overview of compounds that inhibit ABCA1 and ABCG1 protein breakdown, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference Acifran GPR109A agonist — — — Gaidarov et al., 2013 Acipimox GPR109A agonist — — — Gaidarov et al., 2013 ALLN Thiol-protease inhibitor =↑ THP-1 — ↑ THP-1 Arakawa and Yokoyama, 2002; Yokoyama, 2004 Calphostin C PKC inhibitor — — ↓ CHO-K1 ABCG1(+12) Gelissen et al., 2012 ↓ CHO-K1 ABCG1(−12) Diphenoquinone Unknown, probucol metabolite ↑ THP-1 ↑ RAW264.7 ↑ THP-1 Arakawa et al., 2009; Lu et al., 2016; Yakushiji et al., 2016 ↑ RAW264.7 RAW264.7 ↑ HEK293 ↑ apoA-I ↑ Balb/3T3 ↑ HDL ↑ MEFs ↑ Hek293 =↑ Livera ↑ MEFs Exendin-4 GLP-1R agonist ↑↑ 3T3-L1 adipocytes ↑↑ 3T3-L1 adipocytes ↑ 3T3-L1 adipocytes Mostafa et al., 2015; Yin et al., 2016 ↑↑ glomerulib ↑ glomerulib Ezetimibe NPC1L1 inhibitor ↑ VSCMs — — Gong et al., 2014; Kannisto et al., 2014 ↓↓ Liverc ↓↓ Proximal small intestinec Gö6976 PKC inhibitor ↑↑ THP-1 — ↑ THP-1 Iwamoto et al., 2008 Gö6983 PKC inhibitor ↑↑ ↑↑ THP-1 — ↑ THP-1 Iwamoto et al., 2008 Liverc IMM-H007 AMPK agonist ↑ THP-1 — ↑ J774 Huang et al., 2015 ↑ Liverd ↑ THP-1 ↑ RCTc LD211 MC1-R agonist ↑ BMDMd ↑ BMDMd BMDMd Rinne et al., 2017 ↑ apoA-I ↑ HDL Leupeptin Thiol-protease inhibitor =↑ THP-1 — — Arakawa and Yokoyama, 2002 MK-0354 GPR109A agonist = MDMd = MDMd = MDMd Gaidarov et al., 2013 MK-1903 GPR109A agonist ↑ MDMd ↑ MDMd ↑ MDMd Gaidarov et al., 2013 MSG606 MC1-R agonist ↑ BMDMd ↑ BMDMd BMDMd Rinne et al., 2017 = Aortad = Aortad ↑ apoA-I ↑ Liverd ↑ Liverd ↑ HDL N-acetyl cysteine Glutathione synthase stimulator ↓ J774 ↑ J774 J774 Machado et al., 2014 ↓ apoA-I ↑ HDL Niacin GPR109A agonist ↑↑ HepG2 ↑ MDMd ↑ THP-1 Rubic et al., 2004; Siripurkpong and Na-Bangchang, 2009; Wu and Zhao, 2009; Yvan-Charvet et al., 2010a; Zhang et al., 2012; Gaidarov et al., 2013 ↑↑ 3T3-L1 adipocytes ↑ HepG2 ↑ MM6sr ↑ 3T3-L1 adipocytes ↑ MDMd ↑ MM6sr ↑ Monocyted ↑ MDMd ↑↑ Livere Nicardipine Calcium channel blocker — — ↑ THP-1 Suzuki et al., 2004 ↑ RAW264.7 Nifedipine Calcium channel blocker ↑↑ RAW264.7 ↑↑ RAW264.7 ↑ THP-1 Suzuki et al., 2004; Ishii et al., 2010; Zhang et al., 2013b ↑↑ Aorta sinusf RAW264.7 ↑↑ PMa ↑ apoA-I ↑ HDL PD98059 MEK1/2 inhibitor ↑ THP-1 ↑ THP-1 ↓ CHO Zhou et al., 2010; Mulay et al., 2013; Zhang et al., 2016 ↑↑ RAW264.7 ↑↑ RAW264.7 PMd ↓ HuH7 ↓ CHO ↑ HDL ↓ CHO ↓ HEK293 ↑↑ Mouse primary macrop ↑ PMd PKC19-36 PKC inhibitor — — ↓ CHO-K1 ABCG1(+12) Gelissen et al., 2012 ↓ CHO-K1 ABCG1(−12) Rottlerin PKC inhibitor ↑↑ THP-1 — = THP-1 Iwamoto et al., 2008 Spiroquinone Unknown, probucol metabolite ↑ THP-1 ↑ RAW264.7 ↑ THP-1 Yokoyama, 2004; Arakawa et al., 2009; Lu et al., 2016; Yakushiji et al., 2016 ↑ RAW264.7 RAW264.7 ↑ HEK293 ↑ apoA-I ↑ Balb/3T3 = HDL ↑ MEFs ↑ Hek293 =↑ Livera ↑ MEFs Tert-butylhydroquinone Synthetic phenolic antioxidant ↑↑ THP-1 — ↑ THP-1 Lu et al., 2013 U0126 MEK1/2 inhibitor ↑↑ RAW264.7 ↑ THP-1 RAW264.7 Mogilenko et al., 2010; Zhou et al., 2010; Mulay et al., 2013; Xue et al., 2016; Zhang et al., 2016; Liu et al., 2019 ↑↑ HepG2 ↑↑ RAW264.7 ↑ apoA-I ↑↑ PMb ↑↑ Mouse primary macrop ↑ HDL ↑↑ Jurkat ↑ PMd PM ↑↑ PMg ↑ apoA-I ↑↑ Jurkat ↑ HDL Jurkat ↑ apoA-I Verapamil Calcium channel blocker ↑↑ RAW264.7 ↓ RAW264.7 ↑ THP-1 Suzuki et al., 2004 ↑ RAW264.7 Vildagliptin GLP-1R agonist ↑↑ 3T3-L1 adipocytes ↑↑ 3T3-L1 adipocytes ↑ 3T3-L1 adipocytes Mostafa et al., 2015, 2016 ALLN, N-acetyl-leu-leu-norleucinal; GLP-1R, glucagon-like peptide-1 receptor; MDM, monocyte-derived macrophage; MEF, murine embryonic fibroblast; MEK, mitogen-activated protein kinase kinase; NPC1L1, Niemann-Pick C1-like 1; PM, peritoneal macrophages.
↵a New Zealand White rabbits.
↵b apoE−/− C75BL/6 diabetic mice.
↵c apoE−/− C75BL/6 mice.
↵d C75BL/6 mice.
↵e Golden Syrian Hamster.
↵f C3H/He mice.
↵g Sprague Dawley rats.
- TABLE 7
Compounds increasing cAMP levels
Overview of compounds that increase intracellular cAMP levels, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference 6-Benz-cAMP PKA agonist ↑ THP-1 — ↑ THP-1 Bingham et al., 2010 8-Bromo-cAMP cAMP analog =↑ Skin fibroblastsa — ↑ THP-1 Haidar et al., 2002; Lin and Bornfeldt, 2002 ↑ PM ↑ Skin fibroblastsa 8-(4-Chlorophenylthio)adenosine-cAMP cAMP analog ↑ J774.A1 — = THP-1 Sakr et al., 1999; Kellner-Weibel et al., 2003 ↑ J774.A1 ↑ L cells = CHO = Fu5AH = Skin fibroblastsa ↑ Mouse PM 8-pcPT-2′-O-Me-cAMP Epac agonist ↑ THP-1 — ↑ THP-1 Bingham et al., 2010 ATL313 A2AR agonist ↑↑ THP-1 ↑↑ THP-1 — Voloshyna et al., 2013 (Bu)2cAMP cAMP analog ↑ RAW264.7 — ↑ RAW264.7 Manna et al., 2015 CGS-21680 A2AR agonist ↑↑ THP-1 ↑↑ THP-1 ↑ THP-1 Bingham et al., 2010; Voloshyna et al., 2013 Cilomast PDE4 inhibitor ↑ THP-1 — ↑ THP-1 Lin and Bornfeldt, 2002 ↑ J774.A1 ↑ J774.A1 Cilostazol PDE3 inhibitor ↑↑ THP-1 ↑↑ THP-1 ↑ THP-1 Nakaya et al., 2010 ↑↑ RAW264.7 ↑↑ RAW264.7 ↑ RAW264.7 ↑ MDMa ↑ MDMa ↑ MDMa ↑ PMb ↑ RCTb = Liverb = Small intestineb Dibutyrl cyclic AMP cAMP analog ↑ RAW264 ↑ Monocyte-derived macropa ↑ RAW264.7 Abe-Dohmae et al., 2000; Gaidarov et al., 2013 ↑ Monocyte-derived macropa ↑ Monocyte-derived macropa Doxazosin α-A1 adrenergic receptor antagonist ↑↑ THP-1 — ↑ THP-1 Iwamoto et al., 2007; Tsunemi et al., 2014 ↑↑ RAW264.7 ↑ RAW264.7 ↑ NCTC clone 1469 ↑ CHO-K1 ↑↑ Liverb Forskolin Adenylyl cyclase activator ↑ Skin fibroblastsa — ↑ THP-1 Haidar et al., 2002; Lin and Bornfeldt, 2002 ↑ Skin fibroblastsa H89 PKA inhibitor — ↑ CHO-K1 ABCG1(+12) ↑ CHO-K1 ABCG1(+12) Gelissen et al., 2012 = CHO-K1 ABCG1(−12) = CHO-K1 ABCG1(−12) IBMX Nonselective PDE inhibitor — — ↑ THP-1 Haidar et al., 2002; Lin and Bornfeldt, 2002 ↑ Skin fibroblastsa KT5720 PKA inhibitor — — ↑ CHO-K1 ABCG1(+12) Gelissen et al., 2012 = CHO-K1 ABCG1(−12) Methotrexate Dihydrofolate reductase inhibitor ↑ PBMCsa — Chen et al., 2011a Rolipram PDE4-selective inhibitor ↑↑ THP-1 — ↑ THP-1 Lin and Bornfeldt, 2002 ↑ J774.A1 ↑ J774.A1 - TABLE 8
Compounds increasing ABCA1/G1 expression or function by an unknown mechanism
Overview of compounds that increase ABCA1 or ABCG1 expression or function by a yet unknown mechanism, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.
Compound Primary Action ABCA1 ABCG1 Cholesterol Efflux Reference 1-Phenyl-2-Decanoylamino-3-morpholino-1-propanol Glycosylceramide transferase inhibitor ↑↑ Skin fibroblastsa — ↑ Skin fibroblastsa Glaros et al., 2005 ↑ MDMa Aclarubicin Topoisomerase I and II inhibitor ↑↑ HepG2 — — Gao et al., 2008 Anacetrapib CETP inhibitor — — ↑ THP-1 Yvan-Charvet et al., 2010a; Brodeur et al., 2017 ↑ BHK ↑ ABCA1-expressing BHK Daidzein Mitochondrial aldehyde dehydrogenase inhibitor ↑↑ HepG2 — — Gao et al., 2008 Dalcetrapib CETP inhibitor — — ↑ BHK Brodeur et al., 2017 ↑ ABCA1-expressing BHK Ibrutinib NLRP3 inflammasome inhibitor ↑ THP-1 = THP-1 THP-1 Chen et al., 2018 = apoA-I ↑ HDL IMB2026791 Unknown — — ↑ THP-1 Liu et al., 2012 ↑ CHO-ABCA1 ↑ CHO MCC950 NLRP3 inflammasome inhibitor ↑ THP-1 = THP-1 THP-1 Chen et al., 2018 = apoA-I ↑ HDL Metformin Antihyperglycemic agent == RAW264.7 ↑↑ RAW264.7 RAW264.7 He et al., 2019 = apoA-I ↑ HDL N-butyldeoxynojirimycin Glycosylceramide transferase inhibitor — — = Skin fibroblastsa Glaros et al., 2005 Pratensein Unknown ↑↑ HepG2 — — Gao et al., 2008 Pyrromycin Microbial protein synthesis inhbitor ↑↑ HepG2 — — Gao et al., 2008 t-AUCB Soluble epoxide hydrolase inhibitor ↑↑ Liverb == Liverb ↑ 3T3-L1 adipocytes Shen et al., 2015 ↑ Epididymal fatc ↑ RCTb Torcetrapib CEPT inhibitor ↑ THP-1 ↑ THP-1 Yvan-Charvet et al., 2007
In this issue
Increased Cholesterol Efflux To Treat Cardiovascular Disease
Jump to section
- Article
- Visual Overview
- Abstract
- I. Introduction
- II. Reverse Cholesterol Transport Pathway
- III. Apolipoprotein A-I and Apolipoprotein E Mimetics
- IV. Regulation and Pharmacological Manipulation of Nuclear Receptor–Mediated ATP-Binding Cassette A1 and ATP-Binding Cassette G1 Expression
- V. ATP-Binding Cassette A1 and ATP-Binding Cassette G1 mRNA Stability
- VI. ATP-Binding Cassette A1 and ATP-Binding Cassette G1 Protein Degradation as a Target to Increase Cholesterol Efflux
- VII. ATP-Binding Cassette A1 Function and Cyclic Adenosine Monophosphate
- VIII. Increasing Cellular Cholesterol Efflux via Unknown Mechanisms
- IX. Conclusions and Future Directions
- Authorship Contributions
- Footnotes
- Abbreviations
- References
- Figures & Data
- Info & Metrics
- eLetters