FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2153678593> ?p ?o ?g. }

• W2153678593 endingPage "1103" @default.
• W2153678593 startingPage "1101" @default.
• W2153678593 abstract "HomeCirculation ResearchVol. 116, No. 7Small HDL Promotes Cholesterol Efflux by the ABCA1 Pathway in Macrophages Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBSmall HDL Promotes Cholesterol Efflux by the ABCA1 Pathway in MacrophagesImplications for Therapies Targeted to HDL Jay W. Heinecke Jay W. HeineckeJay W. Heinecke From the Department of Medicine, University of Washington, Seattle, WA. Search for more papers by this author Originally published27 Mar 2015https://doi.org/10.1161/CIRCRESAHA.115.306052Circulation Research. 2015;116:1101–1103Clinical and epidemiological studies show a robust, inverse association of high-density lipoprotein (HDL) levels with cardiovascular disease (CVD) risk.1 Moreover, genetically engineered mice provide compelling evidence that HDL is atheroprotective in hypercholesterolemic animal models. These observations have triggered intense interest in targeting HDL for therapeutic intervention.Article, see p 1133Most clinical studies have used HDL-cholesterol (HDL-C) as the metric for quantifying HDL’s cardioprotective effects. However, recent evidence has raised doubts about elevating HDL-C being therapeutic.1 For example, genetic variations that associate with altered HDL-C levels do not strongly associate with altered CVD risk. Also, prospective clinical trials of niacin and cholesteryl ester transfer protein inhibitors (2 drugs that elevate HDL-C levels by different mechanisms) failed to reduce cardiac events in statin-treated subjects with established CVD.1 Moreover, when mice lack certain proteins involved in HDL metabolism—such as SR-B1, the liver receptor for HDL—both HDL-C levels and atherosclerosis increase dramatically.2 Thus, quantifying HDL-C does not necessarily assess HDL’s proposed ability to lower CVD risk.Many lines of evidence indicate that one of HDL’s cardioprotective tasks is to mobilize excess cholesterol from artery wall macrophages.1 For example, mouse studies demonstrate that increased hepatic expression of apolipoprotein A-I, the major HDL protein, increases cholesterol export from macrophages and retards atherosclerosis.Two pathways for sterol export involve the membrane-associated ATP-binding cassette transporters (ABC) ABCA1 and ABCG1, which are highly induced when macrophages accumulate excess cholesterol.1 Thus, atherosclerosis increases markedly in hypercholesterolemic mice when myeloid cells are deficient in ABCA1. Also, humans with ABCA1 deficiency had Tangier’s disease and accumulate macrophages laden with cholesterol in many tissues.3 These observations support the proposal that HDL, ABCA1, and sterol efflux from cells are important regulators of sterol balance in human macrophages.The relevance of sterol efflux from macrophages in humans has been difficult to assess because it accounts for only a small fraction of overall reverse cholesterol transport from peripheral tissues to the liver.1 To measure efflux capacity, de la Llera-Moya et al4 pioneered the use of serum HDL (serum depleted of the atherogenic lipoproteins low-density lipoprotein and very low–density lipoprotein, which deliver cholesterol to macrophages) with cultured J774 macrophages radiolabeled with cholesterol. They demonstrated that the cholesterol efflux capacity of human serum HDL varies markedly, despite similar levels of HDL-C.5 Thus, HDL-C level is not the major determinant of macrophage sterol efflux in this system.Using the same model system,5 investigators found strong, inverse associations between the cholesterol efflux capacity of serum HDL and prevalent coronary artery disease. Differences in efflux capacity of serum HDL correlated with altered efflux by the ABCA1 pathway in macrophages.4,5 Moreover, efflux capacity remained a strong predictor of prevalent coronary artery disease after adjustment for HDL-C levels.5 This study provided the first strong clinical evidence that a proposed functional property of HDL might be more relevant to human atherosclerosis than HDL-C levels.The efflux capacity of serum HDL with J774 macrophages can also be assessed with fluorescently labeled cholesterol, which primarily measures cholesterol export by ABCA1. A recent study of a large, population-based cohort initially free of CVD demonstrated that sterol efflux assessed by this method associates strongly and negatively with the risk of future cardiac events.6 This association persisted after multivariate adjustment, suggesting that impaired HDL function affects incident cardiovascular risk by processes distinct from those involving HDL-C and other traditional lipid risk factors. Taken together,5,6 these observations provide strong evidence that HDL’s capacity to accept cholesterol via ABCA1 is a functional metric, relevant to atheroprotection, that is independent of HDL-C.HDL is not a homogeneous population. It is a collection of particles that range in size from <7 nm to >14 nm and contains >80 different proteins.7 Most HDL particles are spherical with a core of hydrophobic lipids (cholesteryl ester and triglycerides). However, the major initial acceptor for cholesterol excreted by cells seems to be prebeta HDL, a quantitatively minor species of plasma HDL made of poorly lipidated apolipoprotein A-I.Pioneering studies by Francis et al8 demonstrated that lipid-free apolipoprotein A-I promotes cholesterol efflux from cells and that this pathway is defective in Tangier’s disease fibroblasts. Other lipid-free or lipid-poor apolipoproteins can also promote cholesterol efflux by ABCA1. In contrast, lipid-free apolipoprotein A-I fails to promote sterol efflux from cells by the ABCG1 pathway.1 Instead, the major acceptor for free cholesterol export by ABCG1 is spherical HDL. Efflux by ABCG1 increases as the phospholipid surface layer of spherical HDLs enlarges.In this model, lipid-free or poorly lipidated apolipoprotein A-I accepts sterol (and phospholipid) from cells by a pathway involving ABCA1 (Figure A) to become discoidal HDL particles that lack a cholesteryl ester core. Lecithin-cholesterol acyltransferase (LCAT) then converts the newly accepted cholesterol to cholesteryl ester, which—being more hydrophobic—migrates into the core of the nascent HDL particle to generate a more mature spherical HDL.9 This form of HDL becomes an acceptor for cholesterol exported from cells by ABCG1, and this second wave of cholesterol enlarges the HDL particles.Download figureDownload PowerPointFigure. Current (A) and proposed (B) models for how different high-density lipoprotein (HDL) species promote cholesterol efflux from macrophages. Both ABCA1 and ABCG1 are transmembrane proteins but they promote sterol efflux by different mechanisms. ABCA1 exports cholesterol from the plasma membrane to cholesterol acceptors, whereas ABCG1 is an intracellular sterol transporter that enriches the plasma membrane with cholesterol. See the text for additional details. Apo indicates, apolipoprotein; CE, cholesteryl ester; FC, cholesterol; and LCAT, lecithin-cholesterol acyltransferase.A key feature of the current model is that discoidal and more mature forms of HDL do not promote sterol efflux by the ABCA1 pathway (Figure A). The model also implies that increased LCAT activity should promote sterol efflux from macrophages. In this issue, Du et al10 challenge this notion by providing strong evidence that small, dense HDL particles are potent acceptors of cholesterol exported from macrophages by the ABCA1 pathway. Moreover, they show that the major mediator of cholesterol export from macrophages to HDL is ABCA1.Strengths of their studies include using carefully defined sizes of both reconstituted HDL particles and human HDL to examine the affect of size on sterol efflux; quantifying sterol efflux via ABCA1 and ABCG1 from multiple types of macrophages (bone marrow–derived mouse macrophages, a human macrophage cell line, and primary human monocyte–derived macrophages); and quantifying cholesterol efflux with both radiolabeled cholesterol and by sterol mass. The latter point is significant because, under certain circumstances, efflux of radiolabeled cellular cholesterol can be dissociated from changes in overall sterol balance in macrophages. In future studies, it will be critical to determine the mechanistic basis for the variations in efflux capacity seen with different sizes of HDL.The work of Du et al10 suggests a new model for how HDL promotes sterol efflux from macrophages (Figure B): both lipid-free/poorly lipidated apolipoprotein A-I and small HDL particles promote sterol efflux by the ABCA1 pathway. As in the current model, cholesterol derived from both LCAT and ABCG1 increase the size of HDL. Because LCAT converts discoidal HDL and small HDL to larger particles, the enzyme might interfere with macrophage sterol export by the ABCA1 pathway. It is noteworthy that overexpression of LCAT in hypercholesterolemic mice increases both HDL-C and atherosclerosis.11 Moreover, humans deficient in LCAT have very low HDL-C levels but no major increase in CVD risk.7These observations may have important implications for therapies targeted to increase the cardioprotective subspecie(s) of HDL. Importantly, both the drugs that failed to reduce cardiac risk in the clinical trials increase the concentration of HDL2, the large form of HDL.1 If smaller forms of HDL (eg, HDL3) are indeed the main promoters of sterol efflux from macrophages by ABCA1, the drugs may have been ineffective because they failed to increase the concentration of the small HDL particles that promote efflux by this pathway.Two key unresolved issues are the concentrations of the different sizes of HDL subspecies in blood, and how the different subspecies in blood contribute to the sterol efflux capacity of serum HDL with macrophages. The report by Du et al strongly implies that different-sized HDLs have distinct functional capacities and furthermore that small, cholesterol-poor particles play important roles in mobilizing cholesterol from macrophages. HDL levels are generally measured indirectly as the cholesterol content of HDL. Because HDL varies widely in size, the cholesterol content of an HDL particle can vary >10-fold.7 At a given level of HDL-C, it is theoretically possible to have many small cholesterol-poor particles or far fewer large, cholesterol-rich particles. Thus, a key issue confounding the interpretation of HDL-C as a measure of HDL concentration and function is the relative balance between large and small HDL particles. An additional complexity is the difference in the stoichiometry of apolipoprotein A-I in large and small HDL particles, which makes interpretation of apolipoprotein A-I levels (or HDL protein content, the method used by Du et al10) problematic for assessing HDL particle size and concentration. These issues highlight the need for new HDL metrics, which are not biased toward certain subpopulations, such as large cholesterol-rich HDL.We recently developed a method to measure the concentration and size of HDL particles in plasma. Termed calibrated ion mobility analysis, the method uses protein standards to convert ion mobility analysis signal intensity, a relative measurement, to a metric that quantifies the absolute concentration of HDL particles.12 Using this method, we found that the total concentration of HDL particles in plasma to be 13.4 μmol/L, with a mean plasma apolipoprotein A-I value of 48.8 μmol/L, indicating that each HDL particle contains ≈3.6 molecules of apolipoprotein A-I (assuming that all HDL particles contain apolipoprotein A-I). This value is in excellent agreement with the stoichiometry of human HDL determined by other methods.13 Moreover, calibrated ion mobility analysis also yielded values for the size of the HDL subspecies that agree well with those obtained by orthogonal methods.7,12 As expected, both HDL-C and apolipoprotein A-I levels were poor predictors of HDL particle number; both the metrics under-represented small HDLs. In future studies, quantification of HDL size and concentration should be a valuable tool for investigating the roles of specific HDL subspecies and pathways in regulating the efflux capacity of serum HDL.Recent clinical and genetic studies clearly demonstrate that elevating HDL-C does not necessarily reduce CVD risk.1 Therefore, it is time to end the clinical focus on HDL-C and to understand—at the mechanistic level—how HDL’s functional properties contribute to that risk. It will also be important to link changes in HDL’s size and function to genetics and HDL-targeted therapies. The development of new metrics for quantifying HDL function, based on a better understanding of macrophage reverse cholesterol transport, is essential for achieving these goals.AcknowledgmentsThis work was supported by awards from the National Institutes of Health (HL112625, HL108897, P30 DK017047, and P01 HL092969).DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Jay Heinecke, UW Medicine SLU, 850 Republican, PO Box 358055, Seattle, WA 98109. E-mail [email protected].References1. Rader DJ, Tall AR. The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis?Nat Med. 2012; 18:1344–1346. doi: 10.1038/nm.2937.CrossrefMedlineGoogle Scholar2. Trigatti B, Rayburn H, Viñals M, Braun A, Miettinen H, Penman M, Hertz M, Schrenzel M, Amigo L, Rigotti A, Krieger M. Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.Proc Natl Acad Sci U S A. 1999; 96:9322–9327.CrossrefMedlineGoogle Scholar3. Schaefer EJ, Zech LA, Schwartz DE, Brewer HB. Coronary heart disease prevalence and other clinical features in familial high-density lipoprotein deficiency (Tangier disease).Ann Intern Med. 1980; 93:261–266.CrossrefMedlineGoogle Scholar4. de la Llera-Moya M, Drazul-Schrader D, Asztalos BF, Cuchel M, Rader DJ, Rothblat GH. The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages.Arterioscler Thromb Vasc Biol. 2010; 30:796–801. doi: 10.1161/ATVBAHA.109.199158.LinkGoogle Scholar5. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, French BC, Phillips JA, Mucksavage ML, Wilensky RL, Mohler ER, Rothblat GH, Rader DJ. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.N Engl J Med. 2011; 364:127–135. doi: 10.1056/NEJMoa1001689.CrossrefMedlineGoogle Scholar6. Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, Neeland IJ, Yuhanna IS, Rader DR, de Lemos JA, Shaul PW. HDL cholesterol efflux capacity and incident cardiovascular events.N Engl J Med. 2014; 371:2383–2393. doi: 10.1056/NEJMoa1409065.CrossrefMedlineGoogle Scholar7. Rosenson RS, Brewer HB, Chapman MJ, Fazio S, Hussain MM, Kontush A, Krauss RM, Otvos JD, Remaley AT, Schaefer EJ. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events.Clin Chem. 2011; 57:392–410. doi: 10.1373/clinchem.2010.155333.CrossrefMedlineGoogle Scholar8. Francis GA, Knopp RH, Oram JF. Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier Disease.J Clin Invest. 1995; 96:78–87. doi: 10.1172/JCI118082.CrossrefMedlineGoogle Scholar9. Glomset JA, Norum KR, King W. Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: lipid composition and reactivity in vitro.J Clin Invest. 1970; 49:1827–1837. doi: 10.1172/JCI106400.CrossrefMedlineGoogle Scholar10. Du X-M, Kim M-J, Hou L, et al. HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular cholesterol export.Circ Res. 2015; 116:1133–1142. doi: 10.1161/CIRCRESAHA.116.305485.LinkGoogle Scholar11. Bérard AM, Föger B, Remaley A, Shamburek R, Vaisman BL, Talley G, Paigen B, Hoyt RF, Marcovina S, Brewer HB, Santamarina-Fojo S. High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase.Nat Med. 1997; 3:744–749.CrossrefMedlineGoogle Scholar12. Hutchins PM, Ronsein GE, Monette JS, Pamir N, Wimberger J, He Y, Anantharamaiah GM, Kim DS, Ranchalis JE, Jarvik GP, Vaisar T, Heinecke JW. Quantification of HDL particle concentration by calibrated ion mobility analysis.Clin Chem. 2014; 60:1393–1401. doi: 10.1373/clinchem.2014.228114.CrossrefMedlineGoogle Scholar13. Huang R, Silva RA, Jerome WG, Kontush A, Chapman MJ, Curtiss LK, Hodges TJ, Davidson WS. Apolipoprotein A-I structural organization in high-density lipoproteins isolated from human plasma.Nat Struct Mol Biol. 2011; 18:416–422. doi: 10.1038/nsmb.2028.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Esobi I, Olanrewaju O, Echesabal-Chen J and Stamatikos A (2022) Utilizing the LoxP-Stop-LoxP System to Control Transgenic ABC-Transporter Expression In Vitro, Biomolecules, 10.3390/biom12050679, 12:5, (679) Vecchio F, Bisceglia P, Imbimbo B, Lozupone M, Latino R, Resta E, Leone M, Solfrizzi V, Greco A, Daniele A, Watling M, Panza F and Seripa D (2022) Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer’s disease?, Therapeutic Advances in Chronic Disease, 10.1177/20406223221081605, 13, (204062232210816), Online publication date: 1-Jan-2022. Roland M, Godang K, Aukrust P, Henriksen T and Lekva T (2021) Low CETP activity and unique composition of large VLDL and small HDL in women giving birth to small-for-gestational age infants, Scientific Reports, 10.1038/s41598-021-85777-3, 11:1, Online publication date: 1-Dec-2021. Oh H, Jung Y, Moon S, Hwang J, Ban C, Chung J, Chung W and Kweon D (2021) Development of End-Spliced Dimeric Nanodiscs for the Improved Virucidal Activity of a Nanoperforator, ACS Applied Materials & Interfaces, 10.1021/acsami.1c06364, 13:31, (36757-36768), Online publication date: 11-Aug-2021. Vaisar T, Gordon J, Wimberger J, Heinecke J, Hinderliter A, Rubinow D, Girdler S and Rubinow K (2021) Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors, Journal of Clinical Lipidology, 10.1016/j.jacl.2020.11.009, 15:1, (151-161.e0), Online publication date: 1-Jan-2021. Morgan P, Fang L, Lancaster G and Murphy A (2020) Hematopoiesis is regulated by cholesterol efflux pathways and lipid rafts: connections with cardiovascular diseases, Journal of Lipid Research, 10.1194/jlr.TR119000267, 61:5, (667-675), Online publication date: 1-May-2020. Panee J, Pomozi V, Franke A, Le Saux O and Gerschenson M (2020) Chronic marijuana use moderates the correlations of serum cholesterol with systemic mitochondrial function and fluid cognition, Mitochondrion, 10.1016/j.mito.2020.03.006, 52, (135-143), Online publication date: 1-May-2020. Macpherson M, Halvorsen B, Yndestad A, Ueland T, Mollnes T, Berge R, Rashidi A, Otterdal K, Gregersen I, Kong X, Holven K, Aukrust P, Fevang B and Jørgensen S (2019) Impaired HDL Function Amplifies Systemic Inflammation in Common Variable Immunodeficiency, Scientific Reports, 10.1038/s41598-019-45861-1, 9:1, Online publication date: 1-Dec-2019. Tan Y, Ou H, Zhang M, Gong D, Zhao Z, Chen L, Xia X, Mo Z and Tang C Tanshinone IIA Promotes Macrophage Cholesterol Efflux and Attenuates Atherosclerosis of apoE-/- Mice by Omentin-1/ABCA1 Pathway, Current Pharmaceutical Biotechnology, 10.2174/1389201020666190404125213, 20:5, (422-432) Toh R (2019) Assessment of HDL Cholesterol Removal Capacity: Toward Clinical Application, Journal of Atherosclerosis and Thrombosis, 10.5551/jat.RV17028, 26:2, (111-120), Online publication date: 1-Feb-2019. Rubinow K, Vaisar T, Chao J, Heinecke J and Page S (2018) Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men, Journal of Clinical Lipidology, 10.1016/j.jacl.2018.04.013, 12:4, (1072-1082), Online publication date: 1-Jul-2018. Li D, Fawaz M, Morin E, Ming R, Sviridov D, Tang J, Ackermann R, Olsen K, Remaley A and Schwendeman A (2017) Effect of Synthetic High Density Lipoproteins Modification with Polyethylene Glycol on Pharmacokinetics and Pharmacodynamics, Molecular Pharmaceutics, 10.1021/acs.molpharmaceut.7b00734, 15:1, (83-96), Online publication date: 2-Jan-2018. Ronsein G and Heinecke J (2017) Time to ditch HDL-C as a measure of HDL function?, Current Opinion in Lipidology, 10.1097/MOL.0000000000000446, 28:5, (414-418), Online publication date: 1-Oct-2017. Li C, Gong D, Chen L, Zhang M, Xia X, Cheng H, Huang C, Zhao Z, Zheng X, Tang X and Tang C (2017) Puerarin promotes ABCA1-mediated cholesterol efflux and decreases cellular lipid accumulation in THP-1 macrophages, European Journal of Pharmacology, 10.1016/j.ejphar.2017.05.055, 811, (74-86), Online publication date: 1-Sep-2017. Lin X, Hu H, Liu Y, Hu X, Fan X, Zou W, Pan Y, Zhou W, Peng M and Gu C (2017)(2017) Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells, International Journal of Molecular Medicine, 10.3892/ijmm.2017.2949, 39:6, (1452-1460), Online publication date: 1-Jun-2017. Han X, Li H, Jiang Y, Wang H, Li X, Kou J, Zheng Y, Liu Z, Li H, Li J, Dou D, Wang Y, Tian Y and Yang L (2017) Upconversion nanoparticle-mediated photodynamic therapy induces autophagy and cholesterol efflux of macrophage-derived foam cells via ROS generation, Cell Death & Disease, 10.1038/cddis.2017.242, 8:6, (e2864-e2864), Online publication date: 1-Jun-2017. Kaul S, Xu H, Zabalawi M, Maruko E, Fulp B, Bluemn T, Brzoza‐Lewis K, Gerelus M, Weerasekera R, Kallinger R, James R, Zhang Y, Thomas M and Sorci‐Thomas M (2016) Lipid‐Free Apolipoprotein A‐I Reduces Progression of Atherosclerosis by Mobilizing Microdomain Cholesterol and Attenuating the Number of CD131 Expressing Cells: Monitoring Cholesterol Homeostasis Using the Cellular Ester to Total Cholesterol Ratio, Journal of the American Heart Association, 5:11, Online publication date: 26-Oct-2016. Chen W, Sheu W, Tseng P, Lee T, Lee W, Chang P, Chiang A and Amodio N (2016) Modulation of microRNA Expression in Subjects with Metabolic Syndrome and Decrease of Cholesterol Efflux from Macrophages via microRNA-33-Mediated Attenuation of ATP-Binding Cassette Transporter A1 Expression by Statins, PLOS ONE, 10.1371/journal.pone.0154672, 11:5, (e0154672) Pamir N, Hutchins P, Ronsein G, Vaisar T, Reardon C, Getz G, Lusis A and Heinecke J (2016) Proteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway, Journal of Lipid Research, 10.1194/jlr.M063701, 57:2, (246-257), Online publication date: 1-Feb-2016. Ronsein G, Hutchins P, Isquith D, Vaisar T, Zhao X and Heinecke J (2015) Niacin Therapy Increases High-Density Lipoprotein Particles and Total Cholesterol Efflux Capacity But Not ABCA1-Specific Cholesterol Efflux in Statin-Treated Subjects, Arteriosclerosis, Thrombosis, and Vascular Biology, 36:2, (404-411), Online publication date: 1-Feb-2016. Bielicki J (2016) ABCA1 agonist peptides for the treatment of disease, Current Opinion in Lipidology, 10.1097/MOL.0000000000000258, 27:1, (40-46), Online publication date: 1-Feb-2016. March 27, 2015Vol 116, Issue 7 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.115.306052PMID: 25814677 Originally publishedMarch 27, 2015 Keywordsatherosclerosischolesterol metabolismmacrophageEditorialslipid therapylipoproteinsPDF download Advertisement SubjectsChronic Ischemic Heart DiseaseDiagnostic TestingLipids and CholesterolMechanismsPathophysiology" @default.
• W2153678593 created "2016-06-24" @default.
• W2153678593 creator A5035595391 @default.
• W2153678593 date "2015-03-27" @default.
• W2153678593 modified "2023-10-14" @default.
• W2153678593 title "Small HDL Promotes Cholesterol Efflux by the ABCA1 Pathway in Macrophages" @default.
• W2153678593 cites W1964556269 @default.
• W2153678593 cites W1986524045 @default.
• W2153678593 cites W1996546400 @default.
• W2153678593 cites W2009832539 @default.
• W2153678593 cites W2012504949 @default.
• W2153678593 cites W2012650964 @default.
• W2153678593 cites W2055823448 @default.
• W2153678593 cites W2067453762 @default.
• W2153678593 cites W2087250632 @default.
• W2153678593 cites W2109429564 @default.
• W2153678593 cites W2116775019 @default.
• W2153678593 cites W2139962002 @default.
• W2153678593 cites W2141731387 @default.
• W2153678593 doi "https://doi.org/10.1161/circresaha.115.306052" @default.
• W2153678593 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4380245" @default.
• W2153678593 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25814677" @default.
• W2153678593 hasPublicationYear "2015" @default.
• W2153678593 type Work @default.
• W2153678593 sameAs 2153678593 @default.
• W2153678593 citedByCount "28" @default.
• W2153678593 countsByYear W21536785932016 @default.
• W2153678593 countsByYear W21536785932017 @default.
• W2153678593 countsByYear W21536785932018 @default.
• W2153678593 countsByYear W21536785932019 @default.
• W2153678593 countsByYear W21536785932020 @default.
• W2153678593 countsByYear W21536785932021 @default.
• W2153678593 countsByYear W21536785932022 @default.
• W2153678593 countsByYear W21536785932023 @default.
• W2153678593 crossrefType "journal-article" @default.
• W2153678593 hasAuthorship W2153678593A5035595391 @default.
• W2153678593 hasBestOaLocation W21536785931 @default.
• W2153678593 hasConcept C104317684 @default.
• W2153678593 hasConcept C110459506 @default.
• W2153678593 hasConcept C126322002 @default.
• W2153678593 hasConcept C134018914 @default.
• W2153678593 hasConcept C149011108 @default.
• W2153678593 hasConcept C185592680 @default.
• W2153678593 hasConcept C200082930 @default.
• W2153678593 hasConcept C202751555 @default.
• W2153678593 hasConcept C2777704780 @default.
• W2153678593 hasConcept C2778163477 @default.
• W2153678593 hasConcept C2779244956 @default.
• W2153678593 hasConcept C2780072125 @default.
• W2153678593 hasConcept C55493867 @default.
• W2153678593 hasConcept C71924100 @default.
• W2153678593 hasConcept C86803240 @default.
• W2153678593 hasConcept C95444343 @default.
• W2153678593 hasConceptScore W2153678593C104317684 @default.
• W2153678593 hasConceptScore W2153678593C110459506 @default.
• W2153678593 hasConceptScore W2153678593C126322002 @default.
• W2153678593 hasConceptScore W2153678593C134018914 @default.
• W2153678593 hasConceptScore W2153678593C149011108 @default.
• W2153678593 hasConceptScore W2153678593C185592680 @default.
• W2153678593 hasConceptScore W2153678593C200082930 @default.
• W2153678593 hasConceptScore W2153678593C202751555 @default.
• W2153678593 hasConceptScore W2153678593C2777704780 @default.
• W2153678593 hasConceptScore W2153678593C2778163477 @default.
• W2153678593 hasConceptScore W2153678593C2779244956 @default.
• W2153678593 hasConceptScore W2153678593C2780072125 @default.
• W2153678593 hasConceptScore W2153678593C55493867 @default.
• W2153678593 hasConceptScore W2153678593C71924100 @default.
• W2153678593 hasConceptScore W2153678593C86803240 @default.
• W2153678593 hasConceptScore W2153678593C95444343 @default.
• W2153678593 hasIssue "7" @default.
• W2153678593 hasLocation W21536785931 @default.
• W2153678593 hasLocation W21536785932 @default.
• W2153678593 hasLocation W21536785933 @default.
• W2153678593 hasLocation W21536785934 @default.
• W2153678593 hasOpenAccess W2153678593 @default.
• W2153678593 hasPrimaryLocation W21536785931 @default.
• W2153678593 hasRelatedWork W1780633743 @default.
• W2153678593 hasRelatedWork W1990488222 @default.
• W2153678593 hasRelatedWork W2111482014 @default.
• W2153678593 hasRelatedWork W2116775019 @default.
• W2153678593 hasRelatedWork W2123241855 @default.
• W2153678593 hasRelatedWork W2396513904 @default.
• W2153678593 hasRelatedWork W3042960411 @default.
• W2153678593 hasRelatedWork W4233455462 @default.
• W2153678593 hasRelatedWork W4291001774 @default.
• W2153678593 hasRelatedWork W2015878112 @default.
• W2153678593 hasVolume "116" @default.
• W2153678593 isParatext "false" @default.
• W2153678593 isRetracted "false" @default.
• W2153678593 magId "2153678593" @default.
• W2153678593 workType "article" @default.