CoChat
Sign Up
Cited by 11Cholesterol and Lipid MetabolismLipid metabolism and disordersLiver physiology and pathology

Hepatic Lipoprotein Metabolism: Current and Future In Vitro Cell-Based Systems

Open access
Kiss, Izabella, Neuwert, Nicole, Oberle, Raimund, Hengstschläger, Markus, Osmanagic-Myers, Selma, Stangl, Herbert·2025·Biomolecules
DOI 10.3390/biom15070956PMC PMC12292278
Open this paper in CoChat — free accountOpen PDF

Abstract

Changes in hepatic lipoprotein metabolism are responsible for the majority of metabolic dysfunction-associated disorders, including familial hypercholesterolemia (FH), metabolic syndrome (MetS), metabolic dysfunction-associated fatty liver disease (MAFLD), and age-related diseases such as atherosclerosis, a major health burden in modern society. This review aims to advance the understanding of state-of-the-art mechanistic concepts in lipoprotein metabolism, with a particular focus on lipoprotein uptake and secretion and their dysregulation in disease, and to provide a comprehensive overview of experimental models used to study these processes. Human lipoprotein research faces several challenges. First, significant differences in lipoprotein metabolism between humans and other species hinder the reliability of non-human model systems. Additionally, ethical constraints often limit studies on human lipoprotein metabolism using tracers. Lastly, while 2D hepatocyte cell culture systems are widely used, they are commonly of cancerous origins, limiting their physiological relevance and necessitating the use of more physiologically representative models. In this review, we will elaborate on key findings in lipoprotein metabolism, as well as limitations and challenges of currently available study tools, highlighting mechanistic insights throughout discussion of these models. These include human tracer studies, animal studies, 2D tissue culture-based systems derived from cancerous tissue as well as from induced pluripotent stem cells (iPSCs)/embryonic stem cells (ESCs). Finally, we will discuss precision-cut liver slices, liver-on-a-chip models, and, particularly, improved 3D models: (i) spheroids generated from either hepatoma cancer cell lines or primary human hepatocytes and (ii) organoids generated from liver tissues or iPSCs/ESCs. In the last section, we will explore future perspectives on liver-in-a-dish models in studying mechanisms of liver diseases, treatment options, and their applicability in precision medicine approaches. By comparing traditional and advanced models, this review will highlight the future directions of lipoprotein metabolism research, with a focus on the growing potential of 3D liver organoid models.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/biom15070956

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In vitro models express human apolipoproteins, lipoprotein receptors, and lipid transport proteins, providing a metabolically relevant context for studying lipid accumulation pathways relevant to MASLD.

    “In contrast, in vitro models express human apolipoproteins, lipoprotein receptors, and lipid transport proteins [43,44,45,46], providing a metabolically relevant context for studying lipid accumulation pathways relevant to MASLD.”

    From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [43]

    Section 4.5 reports that liver organoids express several apolipoproteins and have lipoprotein receptors, and proposes using them to study lipid-droplet formation and MAFLD progression. The paper discusses lipid transport proteins, but the cited passages do not establish their expression in these in vitro models; that part of the attributed claim remains unsupported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 252 · Cited by 11

Research works printed but not linked: 241

  1. [1]Gugliucci A. The chylomicron saga: Time to focus on postprandial metabolism Front. Endocrinol. 2024 14 1322869 10.3389/fendo.2023.1322869 38303975 PMC10830840 · DOI
  2. [2]Feingold K.R. Lipid and Lipoprotein Metabolism Endocrinol. Metab. Clin. N. Am. 2022 51 437 458 10.1016/j.ecl.2022.02.008 35963623 · DOI
  3. [3]Dietschy J.M. Turley S.D. Spady D.K. Role of liver in the maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans J. Lipid Res. 1993 34 1637 1659 10.1016/S0022-2275(20)35728-X 8245716 · DOI · Paper page
  4. [4]Tiwari S. Siddiqi S.A. Intracellular trafficking and secretion of VLDL Arterioscler. Thromb. Vasc. Biol. 2012 32 1079 1086 10.1161/ATVBAHA.111.241471 22517366 PMC3334296 · DOI
  5. [5]Borén J. Chapman M.J. Krauss R.M. Packard C.J. Bentzon J.F. Binder C.J. Daemen M.J. Demer L.L. Hegele R.A. Nicholls S.J. Low-density lipoproteins cause atherosclerotic cardiovascular disease: Pathophysiological, genetic, and therapeutic insights: A consensus statement from the European Atherosclerosis Society Consensus Panel Eur. Heart J. 2020 41 2313 2330 10.1093/eurheartj/ehz962 32052833 PMC7308544 · DOI · Paper page
  6. [6]Hobbs H.H. Brown M.S. Goldstein J.L. Molecular genetics of the LDL receptor gene in familial hypercholesterolemia Hum. Mutat. 1992 1 445 466 10.1002/humu.1380010602 1301956 · DOI
  7. [7]Nikkila K. Aberg F. Isoniemi H. Transmission of LDLR mutation from donor through liver transplantation resulting in hypercholesterolemia in the recipient Am. J. Transplant. 2014 14 2898 2902 10.1111/ajt.12961 25231171 · DOI
  8. [8]Lin D. Lu Y. Qiu B. Feng M. Luo Y. Xue F. Zhou T. Zhu J. Zhang J. Wang L. The therapeutic effect of liver transplantation in 14 children with homozygous familial hypercholesterolemia: A prospective cohort: Liver transplant for familial hypercholesterolemia J. Clin. Lipidol. 2024 18 e1055 e1066 10.1016/j.jacl.2024.08.008 39294020 · DOI
  9. [9]Lambert G. Sjouke B. Choque B. Kastelein J.J. Hovingh G.K. The PCSK9 decade J. Lipid Res. 2012 53 2515 2524 10.1194/jlr.R026658 22811413 PMC3494258 · DOI
  10. [10]Morales S.V. Mahmood A. Pollard J. Mayne J. Figeys D. Wiseman P.W. The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis Biophys. J. 2023 122 3783 3797 10.1016/j.bpj.2023.08.005 37559362 PMC10541495 · DOI
  11. [11]Havel R.J. Hamilton R.L. Hepatocytic lipoprotein receptors and intracellular lipoprotein catabolism Hepatology 1988 8 1689 1704 10.1002/hep.1840080637 2847970 · DOI
  12. [12]Brown M.S. Goldstein J.L. A receptor-mediated pathway for cholesterol homeostasis Science 1986 232 34 47 10.1126/science.3513311 3513311 · DOI · Paper page
  13. [13]Krieger M. Charting the fate of the “good cholesterol”: Identification and characterization of the high-density lipoprotein receptor SR-BI Annu. Rev. Biochem. 1999 68 523 558 10.1146/annurev.biochem.68.1.523 10872459 · DOI
  14. [14]Diffenderfer M.R. Schaefer E.J. The composition and metabolism of large and small LDL Curr. Opin. Lipidol. 2014 25 221 226 10.1097/MOL.0000000000000067 24811298 · DOI
  15. [15]de Beer M.C. van der Westhuyzen D. Whitaker N.L. Webb N.R. de Beer F.C. SR-BI-mediated selective lipid uptake segregates apoA-I and apoA-II catabolism J. Lipid Res. 2005 46 2143 2150 10.1194/jlr.M500068-JLR200 16061955 · DOI
  16. [16]Wang S. Peng D.Q. Yi Y. The unsolved mystery of apoA-I recycling in adipocyte Lipids Health Dis. 2016 15 35 10.1186/s12944-016-0203-x 26911989 PMC4765186 · DOI
  17. [17]Yvan-Charvet L. Wang N. Tall A.R. Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses Arterioscler. Thromb. Vasc. Biol. 2010 30 139 143 10.1161/ATVBAHA.108.179283 19797709 PMC2812788 · DOI
  18. [18]Lee-Rueckert M. Escola-Gil J.C. Kovanen P.T. HDL functionality in reverse cholesterol transport—Challenges in translating data emerging from mouse models to human disease Biochim. Biophys. Acta 2016 1861 566 583 10.1016/j.bbalip.2016.03.004 26968096 · DOI
  19. [19]Shrestha S. Wu B.J. Guiney L. Barter P.J. Rye K.-A. Cholesteryl ester transfer protein and its inhibitors J. Lipid Res. 2018 59 772 783 10.1194/jlr.R082735 29487091 PMC5928430 · DOI
  20. [20]Semmler G. Baumgartner C. Metz M. Gensluckner S. Habisch H. Hofer H. März W. Offner F. Völkerer A. Petrenko O. Lipid Dysregulation in Tangier Disease: A Case Series and Metabolic Characterization J. Clin. Endocrinol. Metab. 2025 110 e2146 e2156 10.1210/clinem/dgaf131 40037526 PMC12187588 · DOI
  21. [21]Axmann M. Plochberger B. Mikula M. Weber F. Strobl W.M. Stangl H. Plasma Membrane Lipids: An Important Binding Site for All Lipoprotein Classes Membranes 2021 11 882 10.3390/membranes11110882 34832111 PMC8622984 · DOI
  22. [22]Axmann M. Sezgin E. Karner A. Novacek J. Brodesser M.D. Rohrl C. Preiner J. Stangl H. Plochberger B. Receptor-Independent Transfer of Low Density Lipoprotein Cargo to Biomembranes Nano Lett. 2019 19 2562 2567 10.1021/acs.nanolett.9b00319 30848605 PMC6463238 · DOI
  23. [23]Axmann M. Strobl W.M. Plochberger B. Stangl H. Cholesterol transfer at the plasma membrane Atherosclerosis 2019 290 111 117 10.1016/j.atherosclerosis.2019.09.022 31605876 · DOI
  24. [24]Plochberger B. Axmann M. Rohrl C. Weghuber J. Brameshuber M. Rossboth B.K. Mayr S. Ros R. Bittman R. Stangl H. Direct observation of cargo transfer from HDL particles to the plasma membrane Atherosclerosis 2018 277 53 59 10.1016/j.atherosclerosis.2018.08.032 30173079 · DOI
  25. [25]Plochberger B. Rohrl C. Preiner J. Rankl C. Brameshuber M. Madl J. Bittman R. Ros R. Sezgin E. Eggeling C. HDL particles incorporate into lipid bilayers—A combined AFM and single molecule fluorescence microscopy study Sci. Rep. 2017 7 15886 10.1038/s41598-017-15949-7 29162870 PMC5698431 · DOI
  26. [26]Plochberger B. Sych T. Weber F. Novacek J. Axmann M. Stangl H. Sezgin E. Lipoprotein Particles Interact with Membranes and Transfer Their Cargo without Receptors Biochemistry 2020 59 4421 4428 10.1021/acs.biochem.0c00748 33147967 PMC7677925 · DOI
  27. [27]Lund-Katz S. Hammerschlag B. Phillips M.C. Kinetics and mechanism of free cholesterol exchange between human serum high- and low-density lipoproteins Biochemistry 1982 21 2964 2969 10.1021/bi00541a025 7104306 · DOI
  28. [28]Rothblat G.H. Mahlberg F.H. Johnson W.J. Phillips M.C. Apolipoproteins, membrane cholesterol domains, and the regulation of cholesterol efflux J. Lipid Res. 1992 33 1091 1097 10.1016/S0022-2275(20)40761-8 1431592 · DOI
  29. [29]Phillips M.C. Johnson W.J. Rothblat G.H. Mechanisms and consequences of cellular cholesterol exchange and transfer Biochim. Biophys. Acta 1987 906 223 276 10.1016/0304-4157(87)90013-X 3297153 · DOI
  30. [30]Scobey M.W. Johnson F.L. Rudel L.L. Delivery of high-density lipoprotein free and esterified cholesterol to bile by the perfused monkey liver Am. J. Physiol. 1989 257 G644 G652 10.1152/ajpgi.1989.257.4.G644 2801946 · DOI
  31. [31]Schwartz C.C. VandenBroek J.M. Cooper P.S. Lipoprotein cholesteryl ester production, transfer, and output in vivo in humans J. Lipid Res. 2004 45 1594 1607 10.1194/jlr.M300511-JLR200 15145983 · DOI
  32. [32]Schwartz C.C. Berman M. Vlahcevic Z.R. Halloran L.G. Gregory D.H. Swell L. Multicompartmental analysis of cholesterol metabolism in man. Characterization of the hepatic bile acid and biliary cholesterol precursor sites J. Clin. Investig. 1978 61 408 423 10.1172/JCI108952 621281 PMC372552 · DOI
  33. [33]Schwartz C.C. Halloran L.G. Vlahcevic Z.R. Gregory D.H. Swell L. Preferential utilization of free cholesterol from high-density lipoproteins for biliary cholesterol secretion in man Science 1978 200 62 64 10.1126/science.204996 204996 · DOI
  34. [34]Schwartz C.C. Vlahcevic Z.R. Berman M. Meadows J.G. Nisman R.M. Swell L. Central role of high density lipoprotein in plasma free cholesterol metabolism J. Clin. Investig. 1982 70 105 116 10.1172/JCI110582 6953075 PMC370232 · DOI
  35. [35]Schwartz C.C. Zech L.A. VandenBroek J.M. Cooper P.S. Cholesterol kinetics in subjects with bile fistula. Positive relationship between size of the bile acid precursor pool and bile acid synthetic rate J. Clin. Investig. 1993 91 923 938 10.1172/JCI116314 8450070 PMC288045 · DOI
  36. [36]Yelamanchili D. Gillard B.K. Gotto A.M. Jr. Achirica M.C. Nasir K. Remaley A.T. Rosales C. Pownall H.J. HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content J. Lipid Res. 2025 66 100707 10.1016/j.jlr.2024.100707 39566848 PMC11696839 · DOI
  37. [37]Kutyavin V.I. Chawla A. Aster: A New Star in Cholesterol Trafficking Cell 2018 175 307 309 10.1016/j.cell.2018.09.025 30290136 · DOI
  38. [38]Ferrari A. Tontonoz P. Nonvesicular cholesterol transport in physiology J. Clin. Investig. 2025 135 e188127 10.1172/JCI188127 40091839 PMC11910210 · DOI
  39. [39]Ouimet M. Barrett T.J. Fisher E.A. HDL and Reverse Cholesterol Transport Circ. Res. 2019 124 1505 1518 10.1161/CIRCRESAHA.119.312617 31071007 PMC6813799 · DOI
  40. [40]Gracia-Sancho J. Caparrós E. Fernández-Iglesias A. Francés R. Role of liver sinusoidal endothelial cells in liver diseases Nat. Rev. Gastroenterol. Hepatol. 2021 18 411 431 10.1038/s41575-020-00411-3 33589830 · DOI
  41. [41]Li R. Oteiza A. Sørensen K.K. McCourt P. Olsen R. Smedsrød B. Svistounov D. Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins Am. J. Physiol. Gastrointest. Liver Physiol. 2011 300 G71 G81 10.1152/ajpgi.00215.2010 21030611 PMC3025507 · DOI
  42. [42]Van Berkel T.J. De Rijke Y.B. Kruijt J.K. Different fate in vivo of oxidatively modified low density lipoprotein and acetylated low density lipoprotein in rats. Recognition by various scavenger receptors on Kupffer and endothelial liver cells J. Biol. Chem. 1991 266 2282 2289 10.1016/S0021-9258(18)52241-9 1989982 · DOI
  43. [43]Mao H. Kruse L.D. Li R. Oteiza A. Struck E.C. Schürstedt J. Hübner W. Cogger V.C. Le Couteur D. Wolfson D.L. Impact of oxidized low-density lipoprotein on rat liver sinusoidal endothelial cell morphology and function Npj Gut Liver 2024 1 9 10.1038/s44355-024-00009-5 · DOI
  44. [44]Le Couteur D.G. Fraser R. Cogger V.C. McLean A.J. Hepatic pseudocapillarisation and atherosclerosis in ageing Lancet 2002 359 1612 1615 10.1016/S0140-6736(02)08524-0 12047987 · DOI
  45. [45]Grosse L. Bulavin D.V. LSEC model of aging Aging 2020 12 11152 11160 10.18632/aging.103492 32535553 PMC7346042 · DOI
  46. [46]Grosse L. Wagner N. Emelyanov A. Molina C. Lacas-Gervais S. Wagner K.D. Bulavin D.V. Defined p16(High) Senescent Cell Types Are Indispensable for Mouse Healthspan Cell Metab. 2020 32 87 99.e86 10.1016/j.cmet.2020.05.002 32485135 · DOI · Paper page
  47. [47]Mitchell S.J. Huizer-Pajkos A. Cogger V.C. McLachlan A.J. Le Couteur D.G. Jones B. de Cabo R. Hilmer S.N. Age-related pseudocapillarization of the liver sinusoidal endothelium impairs the hepatic clearance of acetaminophen in rats J. Gerontol. A Biol. Sci. Med. Sci. 2011 66 400 408 10.1093/gerona/glq221 21300741 PMC3055277 · DOI
  48. [48]Kraehling J.R. Chidlow J.H. Rajagopal C. Sugiyama M.G. Fowler J.W. Lee M.Y. Zhang X. Ramírez C.M. Park E.J. Tao B. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells Nat. Commun. 2016 7 13516 10.1038/ncomms13516 27869117 PMC5121336 · DOI
  49. [49]Huang L. Chambliss K.L. Gao X. Yuhanna I.S. Behling-Kelly E. Bergaya S. Ahmed M. Michaely P. Luby-Phelps K. Darehshouri A. SR-B1 drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis Nature 2019 569 565 569 10.1038/s41586-019-1140-4 31019307 PMC6631346 · DOI
  50. [50]Fruhwurth S. Pavelka M. Bittman R. Kovacs W.J. Walter K.M. Rohrl C. Stangl H. High-density lipoprotein endocytosis in endothelial cells World J. Biol. Chem. 2013 4 131 140 10.4331/wjbc.v4.i4.131 24340136 PMC3856308 · DOI
  51. [51]Jang E. Robert J. Rohrer L. von Eckardstein A. Lee W.L. Transendothelial transport of lipoproteins Atherosclerosis 2020 315 111 125 10.1016/j.atherosclerosis.2020.09.020 33032832 · DOI
  52. [52]von Eckardstein A. Robert J. Endocytosis, Transcytosis, and Retroendocytosis of HDL: Mechanisms, Pathophysiology, and Options for Clinical Exploitation Arterioscler. Thromb. Vasc. Biol. Online ahead of print 2025 40534556
  53. [53]Wang Y. van der Tuin S. Tjeerdema N. van Dam A.D. Rensen S.S. Hendrikx T. Berbee J.F. Atanasovska B. Fu J. Hoekstra M. Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells Hepatology 2015 62 1710 1722 10.1002/hep.27985 26174697 · DOI
  54. [54]McCuskey R.S. McCuskey P.A. Urbaschek R. Urbaschek B. Kupffer cell function in host defense Rev. Infect. Dis. 1987 9 (Suppl. 5) S616 S619 10.1093/clinids/9.Supplement_5.S616 3317754 · DOI
  55. [55]Naito M. Hasegawa G. Ebe Y. Yamamoto T. Differentiation and function of Kupffer cells Med. Electron. Microsc. 2004 37 16 28 10.1007/s00795-003-0228-x 15057601 · DOI
  56. [56]Takeishi T. Hirano K. Kobayashi T. Hasegawa G. Hatakeyama K. Naito M. The role of Kupffer cells in liver regeneration Arch. Histol. Cytol. 1999 62 413 422 10.1679/aohc.62.413 10678570 · DOI · Paper page
  57. [57]Bilzer M. Roggel F. Gerbes A.L. Role of Kupffer cells in host defense and liver disease Liver Int. 2006 26 1175 1186 10.1111/j.1478-3231.2006.01342.x 17105582 · DOI
  58. [58]Diehl K.L. Vorac J. Hofmann K. Meiser P. Unterweger I. Kuerschner L. Weighardt H. Forster I. Thiele C. Kupffer Cells Sense Free Fatty Acids and Regulate Hepatic Lipid Metabolism in High-Fat Diet and Inflammation Cells 2020 9 2258 10.3390/cells9102258 33050035 PMC7600268 · DOI
  59. [59]Kandhi R. Menendez A. Ramanathan S. Ilangumaran S. Regulation of High-Fat Diet-Induced Liver Fibrosis by SOCS1 Expression in Hepatic Stellate Cells J. Clin. Exp. Hepatol. 2024 14 101280 10.1016/j.jceh.2023.09.001 38076369 PMC10709186 · DOI
  60. [60]Gangireddy V.G.R. Pilkerton C. Xiang J. Tinajero R. Ashcraft A.M. Hepatic Fibrosis and Steatosis in Metabolic Syndrome J. Obes. Metab. Syndr. 2022 31 61 69 10.7570/jomes21062 35283365 PMC8987451 · DOI
  61. [61]Chan D.C. Barrett P.H. Watts G.F. Lipoprotein transport in the metabolic syndrome: Methodological aspects of stable isotope kinetic studies Clin. Sci. 2004 107 221 232 10.1042/CS20040108 15225121 · DOI
  62. [62]Chan D.C. Watts G.F. Ng T.W. Uchida Y. Sakai N. Yamashita S. Barrett P.H. Apolipoprotein B-100 kinetics and static plasma indices of triglyceride-rich lipoprotein metabolism in overweight men Clin. Biochem. 2005 38 806 812 10.1016/j.clinbiochem.2005.05.009 15992790 · DOI
  63. [63]Chan D.C. Barrett P.H. Watts G.F. Lipoprotein transport in the metabolic syndrome: Pathophysiological and interventional studies employing stable isotopy and modelling methods Clin. Sci. 2004 107 233 249 10.1042/CS20040109 15225143 · DOI
  64. [64]Chan D.C. Watts G.F. Redgrave T.G. Mori T.A. Barrett P.H. Apolipoprotein B-100 kinetics in visceral obesity: Associations with plasma apolipoprotein C-III concentration Metabolism 2002 51 1041 1046 10.1053/meta.2002.33339 12145779 · DOI
  65. [65]Chan D.C. Watts G.F. Gan S. Wong A.T. Ooi E.M. Barrett P.H. Nonalcoholic fatty liver disease as the transducer of hepatic oversecretion of very-low-density lipoprotein-apolipoprotein B-100 in obesity Arterioscler. Thromb. Vasc. Biol. 2010 30 1043 1050 10.1161/ATVBAHA.109.202275 20150556 · DOI
  66. [67]Zeng Q. Gong Y. Zhu N. Shi Y. Zhang C. Qin L. Lipids and lipid metabolism in cellular senescence: Emerging targets for age-related diseases Ageing Res. Rev. 2024 97 102294 10.1016/j.arr.2024.102294 38583577 · DOI
  67. [68]Liu J. Zhou L. An Y. Wang Y. Wang G. The atherogenic index of plasma: A novel factor more closely related to non-alcoholic fatty liver disease than other lipid parameters in adults Front. Nutr. 2022 9 954219 10.3389/fnut.2022.954219 36118762 PMC9478109 · DOI
  68. [69]Heeren J. Scheja L. Metabolic-associated fatty liver disease and lipoprotein metabolism Mol. Metab. 2021 50 101238 10.1016/j.molmet.2021.101238 33892169 PMC8324684 · DOI
  69. [71]Ference B.A. Braunwald E. Catapano A.L. The LDL cumulative exposure hypothesis: Evidence and practical applications Nat. Rev. Cardiol. 2024 21 701 716 10.1038/s41569-024-01039-5 38969749 · DOI
  70. [72]Tybjærg-Hansen A. Nordestgaard B.G. Christoffersen M. Triglyceride-rich remnant lipoproteins are more atherogenic than LDL per particle: Is this important? Eur. Heart J. 2023 44 4196 4198 10.1093/eurheartj/ehad419 37403539 · DOI
  71. [73]Berndsen Z.T. Cassidy C.K. The structure of apolipoprotein B100 from human low-density lipoprotein Nature 2025 638 836 843 10.1038/s41586-024-08467-w 39662503 PMC11839476 · DOI · Paper page
  72. [74]Reimund M. Dearborn A.D. Graziano G. Lei H. Ciancone A.M. Kumar A. Holewinski R. Neufeld E.B. O’Reilly F.J. Remaley A.T. Structure of apolipoprotein B100 bound to the low-density lipoprotein receptor Nature 2025 638 829 835 10.1038/s41586-024-08223-0 39663455 · DOI
  73. [75]Khera A.V. Won H.H. Peloso G.M. Lawson K.S. Bartz T.M. Deng X. van Leeuwen E.M. Natarajan P. Emdin C.A. Bick A.G. Diagnostic Yield and Clinical Utility of Sequencing Familial Hypercholesterolemia Genes in Patients With Severe Hypercholesterolemia J. Am. Coll. Cardiol. 2016 67 2578 2589 10.1016/j.jacc.2016.03.520 27050191 PMC5405769 · DOI · Paper page
  74. [76]Sjouke B. Kusters D.M. Kindt I. Besseling J. Defesche J.C. Sijbrands E.J. Roeters van Lennep J.E. Stalenhoef A.F. Wiegman A. de Graaf J. Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: Prevalence, genotype-phenotype relationship, and clinical outcome Eur. Heart J. 2015 36 560 565 10.1093/eurheartj/ehu058 24585268 · DOI
  75. [77]Soutar A.K. Naoumova R.P. Mechanisms of disease: Genetic causes of familial hypercholesterolemia Nat. Clin. Pract. Cardiovasc. Med. 2007 4 214 225 10.1038/ncpcardio0836 17380167 · DOI · Paper page
  76. [78]Vega G.L. Grundy S.M. In vivo evidence for reduced binding of low density lipoproteins to receptors as a cause of primary moderate hypercholesterolemia J. Clin. Investig. 1986 78 1410 1414 10.1172/JCI112729 3771801 PMC423848 · DOI
  77. [79]Innerarity T.L. Weisgraber K.H. Arnold K.S. Mahley R.W. Krauss R.M. Vega G.L. Grundy S.M. Familial defective apolipoprotein B-100: Low density lipoproteins with abnormal receptor binding Proc. Natl. Acad. Sci. USA 1987 84 6919 6923 10.1073/pnas.84.19.6919 3477815 PMC299196 · DOI
  78. [80]Young S.G. Bertics S.J. Curtiss L.K. Witztum J.L. Characterization of an abnormal species of apolipoprotein B, apolipoprotein B-37, associated with familial hypobetalipoproteinemia J. Clin. Investig. 1987 79 1831 1841 10.1172/JCI113025 3584472 PMC424527 · DOI
  79. [81]Simons L.A. Reichl D. Myant N.B. Mancini M. The metabolism of the apoprotein of plasma low density lipoprotein in familial hyperbetalipoproteinaemia in the homozygous form Atherosclerosis 1975 21 283 298 10.1016/0021-9150(75)90087-8 165827 · DOI
  80. [82]Guardamagna O. Abello F. Saracco P. Baracco V. Rolfo E. Pirro M. Endothelial activation, inflammation and premature atherosclerosis in children with familial dyslipidemia Atherosclerosis 2009 207 471 475 10.1016/j.atherosclerosis.2009.06.006 19560772 · DOI
  81. [83]Napoli C. Postiglione A. Triggiani M. Corso G. Palumbo G. Carbone V. Ruocco A. Ambrosio G. Montefusco S. Malorni A. Oxidative structural modifications of low density lipoprotein in homozygous familial hypercholesterolemia Atherosclerosis 1995 118 259 273 10.1016/0021-9150(95)05612-2 8770320 · DOI
  82. [84]Schaefer J.R. Rader D.J. Ikewaki K. Fairwell T. Zech L.A. Kindt M.R. Davignon J. Gregg R.E. Brewer H.B. Jr. In vivo metabolism of apolipoprotein A-I in a patient with homozygous familial hypercholesterolemia Arterioscler. Thromb. 1992 12 843 848 10.1161/01.ATV.12.7.843 1616910 · DOI
  83. [85]Frenais R. Ouguerram K. Maugeais C. Marchini J.S. Benlian P. Bard J.M. Magot T. Krempf M. Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia: A stable isotope study J. Lipid Res. 1999 40 1506 1511 10.1016/S0022-2275(20)33394-0 10428988 · DOI
  84. [86]Bellanger N. Orsoni A. Julia Z. Fournier N. Frisdal E. Duchene E. Bruckert E. Carrie A. Bonnefont-Rousselot D. Pirault J. Atheroprotective reverse cholesterol transport pathway is defective in familial hypercholesterolemia Arterioscler. Thromb. Vasc. Biol. 2011 31 1675 1681 10.1161/ATVBAHA.111.227181 21527752 · DOI
  85. [87]Schmidt K. Noureen A. Kronenberg F. Utermann G. Structure, function, and genetics of lipoprotein (a) J. Lipid Res. 2016 57 1339 1359 10.1194/jlr.R067314 27074913 PMC4959873 · DOI
  86. [88]Cain W.J. Millar J.S. Himebauch A.S. Tietge U.J. Maugeais C. Usher D. Rader D.J. Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a] J. Lipid Res. 2005 46 2681 2691 10.1194/jlr.M500249-JLR200 16150825 · DOI
  87. [89]Siddiqui H. Yevstigneyev N. Madani G. McCormick S. Approaches to Visualising Endocytosis of LDL-Related Lipoproteins Biomolecules 2022 12 158 10.3390/biom12020158 35204658 PMC8961563 · DOI
  88. [90]McCormick S.P.A. Schneider W.J. Lipoprotein(a) catabolism: A case of multiple receptors Pathology 2019 51 155 164 10.1016/j.pathol.2018.11.003 30595508 · DOI
  89. [91]Havekes L. Vermeer B.J. Brugman T. Emeis J. Binding of LP(a) to the low density lipoprotein receptor of human fibroblasts FEBS Lett. 1981 132 169 173 10.1016/0014-5793(81)81153-2 6271586 · DOI
  90. [92]Romagnuolo R. Scipione C.A. Boffa M.B. Marcovina S.M. Seidah N.G. Koschinsky M.L. Lipoprotein(a) catabolism is regulated by proprotein convertase subtilisin/kexin type 9 through the low density lipoprotein receptor J. Biol. Chem. 2015 290 11649 11662 10.1074/jbc.M114.611988 25778403 PMC4416867 · DOI
  91. [93]Romagnuolo R. Scipione C.A. Marcovina S.M. Gemin M. Seidah N.G. Boffa M.B. Koschinsky M.L. Roles of the low density lipoprotein receptor and related receptors in inhibition of lipoprotein(a) internalization by proprotein convertase subtilisin/kexin type 9 PLoS ONE 2017 12 e0180869 10.1371/journal.pone.0180869 28750079 PMC5531514 · DOI
  92. [94]Hofmann S.L. Eaton D.L. Brown M.S. McConathy W.J. Goldstein J.L. Hammer R.E. Overexpression of human low density lipoprotein receptors leads to accelerated catabolism of Lp(a) lipoprotein in transgenic mice J. Clin. Investig. 1990 85 1542 1547 10.1172/JCI114602 2139667 PMC296603 · DOI
  93. [95]Lingenhel A. Kraft H.G. Kotze M. Peeters A.V. Kronenberg F. Kruse R. Utermann G. Concentrations of the atherogenic Lp(a) are elevated in FH Eur. J. Hum. Genet. 1998 6 50 60 10.1038/sj.ejhg.5200152 9781014 · DOI
  94. [96]Carmena R. Lussier-Cacan S. Roy M. Minnich A. Lingenhel A. Kronenberg F. Davignon J. Lp(a) levels and atherosclerotic vascular disease in a sample of patients with familial hypercholesterolemia sharing the same gene defect Arterioscler. Thromb. Vasc. Biol. 1996 16 129 136 10.1161/01.ATV.16.1.129 8548413 · DOI
  95. [97]Yang X.-P. Amar M.J. Vaisman B. Bocharov A.V. Vishnyakova T.G. Freeman L.A. Kurlander R.J. Patterson A.P. Becker L.C. Remaley A.T. Scavenger receptor-BI is a receptor for lipoprotein(a) J. Lipid Res. 2013 54 2450 2457 10.1194/jlr.M038877 23812625 PMC3735942 · DOI
  96. [98]Sharma M. Von Zychlinski-Kleffmann A. Porteous C.M. Jones G.T. Williams M.J. McCormick S.P. Lipoprotein (a) upregulates ABCA1 in liver cells via scavenger receptor-B1 through its oxidized phospholipids J. Lipid Res. 2015 56 1318 1328 10.1194/jlr.M056150 25852127 PMC4479336 · DOI
  97. [99]Borén J. Packard C.J. Binder C.J. Apolipoprotein B-containing lipoproteins in atherogenesis Nat. Rev. Cardiol. 2025 22 399 413 10.1038/s41569-024-01111-0 39743565 · DOI
  98. [100]van der Valk F.M. Bekkering S. Kroon J. Yeang C. Van den Bossche J. van Buul J.D. Ravandi A. Nederveen A.J. Verberne H.J. Scipione C. Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans Circulation 2016 134 611 624 10.1161/CIRCULATIONAHA.116.020838 27496857 PMC4995139 · DOI
  99. [101]Kronenberg F. Mora S. Stroes E.S.G. Ference B.A. Arsenault B.J. Berglund L. Dweck M.R. Koschinsky M. Lambert G. Mach F. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement Eur. Heart J. 2022 43 3925 3946 10.1093/eurheartj/ehac361 36036785 PMC9639807 · DOI · Paper page
  100. [102]Björnson E. Adiels M. Taskinen M.R. Burgess S. Chapman M.J. Packard C.J. Borén J. Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis J. Am. Coll. Cardiol. 2024 83 385 395 10.1016/j.jacc.2023.10.039 38233012 PMC7616706 · DOI
  101. [103]Roudaut M. Caillaud A. Souguir Z. Bray L. Girardeau A. Rimbert A. Croyal M. Lambert G. Patitucci M. Delpouve G. Human induced pluripotent stem cells-derived liver organoids grown on a Biomimesys® hyaluronic acid-based hydroscaffold as a new model for studying human lipoprotein metabolism Bioeng. Transl. Med. 2024 9 e10659 10.1002/btm2.10659 39036087 PMC11256179 · DOI
  102. [104]Boren J. Taskinen M.R. Adiels M. Kinetic studies to investigate lipoprotein metabolism J. Intern. Med. 2012 271 166 173 10.1111/j.1365-2796.2011.02497.x 22142374 · DOI
  103. [106]Getz G.S. Reardon C.A. Animal models of atherosclerosis Arterioscler. Thromb. Vasc. Biol. 2012 32 1104 1115 10.1161/ATVBAHA.111.237693 22383700 PMC3331926 · DOI
  104. [107]Gistera A. Ketelhuth D.F.J. Malin S.G. Hansson G.K. Animal Models of Atherosclerosis-Supportive Notes and Tricks of the Trade Circ. Res. 2022 130 1869 1887 10.1161/CIRCRESAHA.122.320263 35679358 · DOI
  105. [108]Ishibashi S. Brown M.S. Goldstein J.L. Gerard R.D. Hammer R.E. Herz J. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery J. Clin. Investig. 1993 92 883 893 10.1172/JCI116663 8349823 PMC294927 · DOI
  106. [109]Zhang S.H. Reddick R.L. Piedrahita J.A. Maeda N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E Science 1992 258 468 471 10.1126/science.1411543 1411543 · DOI · Paper page
  107. [110]Plump A.S. Smith J.D. Hayek T. Aalto-Setala K. Walsh A. Verstuyft J.G. Rubin E.M. Breslow J.L. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells Cell 1992 71 343 353 10.1016/0092-8674(92)90362-G 1423598 · DOI · Paper page
  108. [111]Dillard A. Matthan N.R. Lichtenstein A.H. Use of hamster as a model to study diet-induced atherosclerosis Nutr. Metab. 2010 7 89 10.1186/1743-7075-7-89 PMC3004901 21143982 · DOI
  109. [112]Fernandez M.L. Volek J.S. Guinea pigs: A suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation Nutr. Metab. 2006 3 17 10.1186/1743-7075-3-17 16566831 PMC1435897 · DOI
  110. [113]Clay M.A. Hopkins G.J. Ehnholm C.P. Barter P.J. The rabbit as an animal model of hepatic lipase deficiency Biochim. Et Biophys. Acta 1989 1002 173 181 10.1016/0005-2760(89)90284-1 2930766 · DOI
  111. [114]Rudel L.L. Bond M.G. Bullock B.C. LDL heterogeneity and atherosclerosis in nonhuman primates Ann. N. Y Acad. Sci. 1985 454 248 253 10.1111/j.1749-6632.1985.tb11864.x 3865611 · DOI
  112. [115]Kingsley D.M. Krieger M. Receptor-mediated endocytosis of low density lipoprotein: Somatic cell mutants define multiple genes required for expression of surface-receptor activity Proc. Natl. Acad. Sci. USA 1984 81 5454 5458 10.1073/pnas.81.17.5454 6089204 PMC391723 · DOI
  113. [116]Chang T.Y. Hasan M.T. Chin J. Chang C.C. Spillane D.M. Chen J. Chinese hamster ovary cell mutants affecting cholesterol metabolism Curr. Opin. Lipidol. 1997 8 65 71 10.1097/00041433-199704000-00003 9183543 · DOI
  114. [117]Harder C.J. Vassiliou G. McBride H.M. McPherson R. Hepatic SR-BI-mediated cholesteryl ester selective uptake occurs with unaltered efficiency in the absence of cellular energy J. Lipid Res. 2006 47 492 503 10.1194/jlr.M500444-JLR200 16339112 · DOI
  115. [118]Goldstein J.L. Dana S.E. Brown M.S. Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia Proc. Natl. Acad. Sci. USA 1974 71 4288 4292 10.1073/pnas.71.11.4288 4373706 PMC433867 · DOI
  116. [119]Hoeg J.M. Demosky S.J. Jr. Lackner K.J. Osborne J.C. Jr. Oliver C. Brewer H.B. Jr. The expressed human hepatic receptor for low-density lipoproteins differs from the fibroblast low-density lipoprotein receptor Biochim. Biophys. Acta 1986 876 13 21 10.1016/0005-2760(86)90312-7 3081041 · DOI
  117. [120]Sparrow C.P. Pittman R.C. Cholesterol esters selectively taken up from high-density lipoproteins are hydrolyzed extralysosomally Biochim. Biophys. Acta 1990 1043 203 210 10.1016/0005-2760(90)90297-B 2317530 · DOI
  118. [121]Rinninger F. Pittman R.C. The selective uptake of HDL cholesteryl esters and its role in reverse cholesterol transport Agents Actions Suppl. 1988 26 181 187 3265276
  119. [122]Goldstein J.L. Brown M.S. Familial hypercholesterolemia: Identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol Proc. Natl. Acad. Sci. USA 1973 70 2804 2808 10.1073/pnas.70.10.2804 4355366 PMC427113 · DOI
  120. [123]Hoeg J.M. Edge S.B. Demosky S.J. Jr. Starzl T.E. Triche T. Gregg R.E. Brewer H.B. Jr. Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects Biochim. Et Biophys. Acta 1986 876 646 657 10.1016/0005-2760(86)90054-8 PMC3006434 3707989 · DOI
  121. [124]Rinninger F. Pittman R.C. Regulation of the selective uptake of high density lipoprotein-associated cholesteryl esters by human fibroblasts and Hep G2 hepatoma cells J. Lipid Res. 1988 29 1179 1194 10.1016/S0022-2275(20)38450-9 2846735 · DOI
  122. [125]Heeren J. Beisiegel U. Grewal T. Apolipoprotein E recycling: Implications for dyslipidemia and atherosclerosis Arterioscler. Thromb. Vasc. Biol. 2006 26 442 448 10.1161/01.ATV.0000201282.64751.47 16373604 · DOI
  123. [126]Pittman R.C. Knecht T.P. Rosenbaum M.S. Taylor C.A. Jr. A nonendocytotic mechanism for the selective uptake of high density lipoprotein-associated cholesterol esters J. Biol. Chem. 1987 262 2443 2450 10.1016/S0021-9258(18)61524-8 2434485 · DOI
  124. [127]Rohrl C. Stangl H. HDL endocytosis and resecretion Biochim. Biophys. Acta 2013 1831 1626 1633 10.1016/j.bbalip.2013.07.014 23939397 PMC3795453 · DOI
  125. [128]Cruz P.M. Mo H. McConathy W.J. Sabnis N. Lacko A.G. The role of cholesterol metabolism and cholesterol transport in carcinogenesis: A review of scientific findings, relevant to future cancer therapeutics Front. Pharmacol. 2013 4 119 10.3389/fphar.2013.00119 24093019 PMC3782849 · DOI
  126. [129]Blidisel A. Marcovici I. Coricovac D. Hut F. Dehelean C.A. Cretu O.M. Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective Cancers 2021 13 3651 10.3390/cancers13153651 34359553 PMC8344976 · DOI
  127. [130]Heeren J. Grewal T. Laatsch A. Rottke D. Rinninger F. Enrich C. Beisiegel U. Recycling of apoprotein E is associated with cholesterol efflux and high density lipoprotein internalization J. Biol. Chem. 2003 278 14370 14378 10.1074/jbc.M209006200 12584196 · DOI
  128. [133]Rhainds D. Brodeur M. Lapointe J. Charpentier D. Falstrault L. Brissette L. The role of human and mouse hepatic scavenger receptor class B type I (SR-BI) in the selective uptake of low-density lipoprotein-cholesteryl esters Biochemistry 2003 42 7527 7538 10.1021/bi026949a 12809509 · DOI
  129. [134]Rohrl C. Meisslitzer-Ruppitsch C. Bittman R. Li Z. Pabst G. Prassl R. Strobl W. Neumuller J. Ellinger A. Pavelka M. Combined light and electron microscopy using diaminobenzidine photooxidation to monitor trafficking of lipids derived from lipoprotein particles Curr. Pharm. Biotechnol. 2012 13 331 340 10.2174/138920112799095338 21470121 PMC3855193 · DOI
  130. [135]Rohrl C. Pagler T.A. Strobl W. Ellinger A. Neumuller J. Pavelka M. Stangl H. Meisslitzer-Ruppitsch C. Characterization of endocytic compartments after holo-high density lipoprotein particle uptake in HepG2 cells Histochem. Cell Biol. 2010 133 261 272 10.1007/s00418-009-0672-3 20039053 PMC3182552 · DOI
  131. [136]Rohrl C. Eigner K. Fruhwurth S. Stangl H. Bile acids reduce endocytosis of high-density lipoprotein (HDL) in HepG2 cells PLoS ONE 2014 9 e102026 10.1371/journal.pone.0102026 25010412 PMC4092120 · DOI
  132. [137]Gerets H.H.J. Tilmant K. Gerin B. Chanteux H. Depelchin B.O. Dhalluin S. Atienzar F.A. Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins Cell Biol. Toxicol. 2012 28 69 87 10.1007/s10565-011-9208-4 22258563 PMC3303072 · DOI · Paper page
  133. [138]Zhou B. Ho S.S. Greer S.U. Spies N. Bell J.M. Zhang X. Zhu X. Arthur J.G. Byeon S. Pattni R. Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2 Nucleic Acids Res. 2019 47 3846 3861 10.1093/nar/gkz169 30864654 PMC6486628 · DOI · Paper page
  134. [139]Thrift R.N. Forte T.M. Cahoon B.E. Shore V.G. Characterization of lipoproteins produced by the human liver cell line, Hep G2, under defined conditions J. Lipid Res. 1986 27 236 250 10.1016/S0022-2275(20)38829-5 3016129 · DOI
  135. [140]Olsavsky K.M. Page J.L. Johnson M.C. Zarbl H. Strom S.C. Omiecinski C.J. Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues Toxicol. Appl. Pharmacol. 2007 222 42 56 10.1016/j.taap.2007.03.032 17512962 PMC2974173 · DOI
  136. [141]Guo L. Dial S. Shi L. Branham W. Liu J. Fang J.L. Green B. Deng H. Kaput J. Ning B. Similarities and differences in the expression of drug-metabolizing enzymes between human hepatic cell lines and primary human hepatocytes Drug Metab. Dispos. 2011 39 528 538 10.1124/dmd.110.035873 21149542 PMC3061558 · DOI · Paper page
  137. [142]Kvist A.J. Kanebratt K.P. Walentinsson A. Palmgren H. O’Hara M. Björkbom A. Andersson L.C. Ahlqvist M. Andersson T.B. Critical differences in drug metabolic properties of human hepatic cellular models, including primary human hepatocytes, stem cell derived hepatocytes, and hepatoma cell lines Biochem. Pharmacol. 2018 155 124 140 10.1016/j.bcp.2018.06.026 29953844 · DOI
  138. [143]Graf J. Gautam A. Boyer J.L. Isolated rat hepatocyte couplets: A primary secretory unit for electrophysiologic studies of bile secretory function Proc. Natl. Acad. Sci. USA 1984 81 6516 6520 10.1073/pnas.81.20.6516 6149546 PMC391955 · DOI
  139. [144]Gautam A. Ng O.C. Boyer J.L. Isolated rat hepatocyte couplets in short-term culture: Structural characteristics and plasma membrane reorganization Hepatology 1987 7 216 223 10.1002/hep.1840070203 3557300 · DOI
  140. [145]Rowe C. Gerrard D.T. Jenkins R. Berry A. Durkin K. Sundstrom L. Goldring C.E. Park B.K. Kitteringham N.R. Hanley K.P. Proteome-wide analyses of human hepatocytes during differentiation and dedifferentiation Hepatology 2013 58 799 809 10.1002/hep.26414 23526496 PMC3842115 · DOI · Paper page
  141. [146]Ling J. Lewis J. Douglas D. Kneteman N.M. Vance D.E. Characterization of lipid and lipoprotein metabolism in primary human hepatocytes Biochim. Biophys. Acta 2013 1831 387 397 10.1016/j.bbalip.2012.08.012 22951416 · DOI
  142. [147]Huggett Z.J. Smith A. De Vivo N. Gomez D. Jethwa P. Brameld J.M. Bennett A. Salter A.M. A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines to Model the Effects of Fatty Acids, Fructose and Glucose on Liver Cell Lipid Accumulation Nutrients 2023 15 40 10.3390/nu15010040 36615698 PMC9824391 · DOI · Paper page
  143. [148]Gissen P. Arias I.M. Structural and functional hepatocyte polarity and liver disease J. Hepatol. 2015 63 1023 1037 10.1016/j.jhep.2015.06.015 26116792 PMC4582071 · DOI
  144. [149]Geraud C. Schledzewski K. Demory A. Klein D. Kaus M. Peyre F. Sticht C. Evdokimov K. Lu S. Schmieder A. Liver sinusoidal endothelium: A microenvironment-dependent differentiation program in rat including the novel junctional protein liver endothelial differentiation-associated protein-1 Hepatology 2010 52 313 326 10.1002/hep.23618 20578158 · DOI · Paper page
  145. [150]Si-Tayeb K. Idriss S. Champon B. Caillaud A. Pichelin M. Arnaud L. Lemarchand P. Le May C. Zibara K. Cariou B. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia Dis. Model. Mech. 2016 9 81 90 10.1242/dmm.022277 26586530 PMC4728336 · DOI
  146. [151]Cayo M.A. Cai J. DeLaForest A. Noto F.K. Nagaoka M. Clark B.S. Collery R.F. Si-Tayeb K. Duncan S.A. JD induced pluripotent stem cell-derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia Hepatology 2012 56 2163 2171 10.1002/hep.25871 22653811 PMC3900031 · DOI
  147. [152]Caron J. Pene V. Tolosa L. Villaret M. Luce E. Fourrier A. Heslan J.M. Saheb S. Bruckert E. Gomez-Lechon M.J. Low-density lipoprotein receptor-deficient hepatocytes differentiated from induced pluripotent stem cells allow familial hypercholesterolemia modeling, CRISPR/Cas-mediated genetic correction, and productive hepatitis C virus infection Stem Cell Res. Ther. 2019 10 221 10.1186/s13287-019-1342-6 31358055 PMC6664765 · DOI
  148. [153]Si-Tayeb K. Lemaigre F.P. Duncan S.A. Organogenesis and development of the liver Dev. Cell 2010 18 175 189 10.1016/j.devcel.2010.01.011 20159590 · DOI · Paper page
  149. [154]Koui Y. Kido T. Ito T. Oyama H. Chen S.W. Katou Y. Shirahige K. Miyajima A. An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-Parenchymal Cells Stem Cell Rep. 2017 9 490 498 10.1016/j.stemcr.2017.06.010 PMC5549957 28757162 · DOI
  150. [155]Takayama K. Inamura M. Kawabata K. Sugawara M. Kikuchi K. Higuchi M. Nagamoto Y. Watanabe H. Tashiro K. Sakurai F. Generation of metabolically functioning hepatocytes from human pluripotent stem cells by FOXA2 and HNF1alpha transduction J. Hepatol. 2012 57 628 636 10.1016/j.jhep.2012.04.038 22659344 · DOI
  151. [156]Du C. Feng Y. Qiu D. Xu Y. Pang M. Cai N. Xiang A.P. Zhang Q. Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails Stem Cell Res. Ther. 2018 9 58 10.1186/s13287-018-0794-4 29523187 PMC5845228 · DOI
  152. [157]Nagamoto Y. Tashiro K. Takayama K. Ohashi K. Kawabata K. Sakurai F. Tachibana M. Hayakawa T. Furue M.K. Mizuguchi H. The promotion of hepatic maturation of human pluripotent stem cells in 3D co-culture using type I collagen and Swiss 3T3 cell sheets Biomaterials 2012 33 4526 4534 10.1016/j.biomaterials.2012.03.011 22445253 · DOI
  153. [158]Takayama K. Kawabata K. Nagamoto Y. Kishimoto K. Tashiro K. Sakurai F. Tachibana M. Kanda K. Hayakawa T. Furue M.K. 3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing Biomaterials 2013 34 1781 1789 10.1016/j.biomaterials.2012.11.029 23228427 · DOI
  154. [159]Bhattacharya M. Malinen M.M. Lauren P. Lou Y.-R. Kuisma S.W. Kanninen L. Lille M. Corlu A. GuGuen-Guillouzo C. Ikkala O. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture J. Control. Release 2012 164 291 298 10.1016/j.jconrel.2012.06.039 22776290 · DOI
  155. [160]Jalil S. Keskinen T. Maldonado R. Sokka J. Trokovic R. Otonkoski T. Wartiovaara K. Simultaneous high-efficiency base editing and reprogramming of patient fibroblasts Stem Cell Rep. 2021 16 3064 3075 10.1016/j.stemcr.2021.10.017 PMC8693657 34822772 · DOI
  156. [161]Okada H. Nakanishi C. Yoshida S. Shimojima M. Yokawa J. Mori M. Tada H. Yoshimuta T. Hayashi K. Yamano T. Function and Immunogenicity of Gene-corrected iPSC-derived Hepatocyte-Like Cells in Restoring Low Density Lipoprotein Uptake in Homozygous Familial Hypercholesterolemia Sci. Rep. 2019 9 4695 10.1038/s41598-019-41056-w 30886174 PMC6423040 · DOI
  157. [162]Smiriglia A. Lorito N. Bacci M. Subbiani A. Bonechi F. Comito G. Kowalik M.A. Perra A. Morandi A. Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease Cell Death Dis. 2025 16 57 10.1038/s41419-025-07331-7 39890799 PMC11785963 · DOI
  158. [163]Tavian D. Missaglia S. Castagnetta M. Degiorgio D. Pennisi E.M. Coleman R.A. Dell’Era P. Mora C. Angelini C. Coviello D.A. Generation of induced Pluripotent Stem Cells as disease modelling of NLSDM Mol. Genet. Metab. 2017 121 28 34 10.1016/j.ymgme.2017.03.009 28391974 PMC5434246 · DOI
  159. [164]Doueiry C. Kappler C.S. Martinez-Morant C. Duncan S.A. A PNPLA3-Deficient iPSC-Derived Hepatocyte Screen Identifies Pathways to Potentially Reduce Steatosis in Metabolic Dysfunction-Associated Fatty Liver Disease Int. J. Mol. Sci. 2024 25 7277 10.3390/ijms25137277 39000384 PMC11242544 · DOI
  160. [165]Liu J.T. Doueiry C. Jiang Y.L. Blaszkiewicz J. Lamprecht M.P. Heslop J.A. Peterson Y.K. Carten J.D. Traktman P. Yuan Y. A human iPSC-derived hepatocyte screen identifies compounds that inhibit production of Apolipoprotein B Commun. Biol. 2023 6 452 10.1038/s42003-023-04739-9 37095219 PMC10125972 · DOI
  161. [166]Cayo M.A. Mallanna S.K. Di Furio F. Jing R. Tolliver L.B. Bures M. Urick A. Noto F.K. Pashos E.E. Greseth M.D. A Drug Screen using Human iPSC-Derived Hepatocyte-like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia Cell Stem Cell 2017 20 478 489.e475 10.1016/j.stem.2017.01.011 28388428 PMC5385853 · DOI
  162. [167]Blaszkiewicz J. Duncan S.A. Use of stem cell-derived hepatocytes to model liver disease J. Hepatol. 2024 80 826 828 10.1016/j.jhep.2023.11.029 38365506 · DOI
  163. [168]Deguchi S. Takayama K. Mizuguchi H. Generation of Human Induced Pluripotent Stem Cell-Derived Hepatocyte-Like Cells for Cellular Medicine Biol. Pharm. Bull. 2020 43 608 615 10.1248/bpb.b19-00740 32238703 · DOI
  164. [169]Si-Tayeb K. Noto F.K. Nagaoka M. Li J. Battle M.A. Duris C. North P.E. Dalton S. Duncan S.A. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells Hepatology 2010 51 297 305 10.1002/hep.23354 19998274 PMC2946078 · DOI · Paper page
  165. [170]Si-Tayeb K. Noto F.K. Sepac A. Sedlic F. Bosnjak Z.J. Lough J.W. Duncan S.A. Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors BMC Dev. Biol. 2010 10 81 10.1186/1471-213X-10-81 20682060 PMC2923111 · DOI
  166. [171]Zanoni P. Khetarpal S.A. Larach D.B. Hancock-Cerutti W.F. Millar J.S. Cuchel M. DerOhannessian S. Kontush A. Surendran P. Saleheen D. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease Science 2016 351 1166 1171 10.1126/science.aad3517 26965621 PMC4889017 · DOI · Paper page
  167. [172]Ramakrishnan V.M. Yang J.Y. Tien K.T. McKinley T.R. Bocard B.R. Maijub J.G. Burchell P.O. Williams S.K. Morris M.E. Hoying J.B. Restoration of Physiologically Responsive Low-Density Lipoprotein Receptor-Mediated Endocytosis in Genetically Deficient Induced Pluripotent Stem Cells Sci. Rep. 2015 5 13231 10.1038/srep13231 26307169 PMC4549683 · DOI
  168. [173]Kerr A.G. Tam L.C. Hale A.B. Cioroch M. Douglas G. Channon K.M. Wade-Martins R. Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia Mol. Ther. Nucleic Acids 2016 5 e383 10.1038/mtna.2016.86 27824334 PMC5155321 · DOI
  169. [174]Koui Y. Kido T. Using human induced pluripotent stem cell-derived liver cells to investigate the mechanisms of liver fibrosis in vitro Biochem. Soc. Trans. 2023 51 1271 1277 10.1042/BST20221421 37264940 PMC10317154 · DOI
  170. [175]Tian S.P. Ge J.Y. Song Y.M. Yu X.Q. Chen W.H. Chen Y.Y. Ye D. Zheng Y.W. A novel efficient strategy to generate liver sinusoidal endothelial cells from human pluripotent stem cells Sci. Rep. 2024 14 13831 10.1038/s41598-024-64195-1 38879647 PMC11180100 · DOI
  171. [176]Tasnim F. Xing J. Huang X. Mo S. Wei X. Tan M.H. Yu H. Generation of mature kupffer cells from human induced pluripotent stem cells Biomaterials 2019 192 377 391 10.1016/j.biomaterials.2018.11.016 30497023 · DOI
  172. [177]Poulis N. Martin M. Hoerstrup S.P. Emmert M.Y. Fioretta E.S. Development of an iPSC-derived tissue-resident macrophage-based platform for the in vitro immunocompatibility assessment of human tissue engineered matrices Sci. Rep. 2024 14 12171 10.1038/s41598-024-62745-1 38806547 PMC11133401 · DOI
  173. [178]Gage B.K. Liu J.C. Innes B.T. MacParland S.A. McGilvray I.D. Bader G.D. Keller G.M. Generation of Functional Liver Sinusoidal Endothelial Cells from Human Pluripotent Stem-Cell-Derived Venous Angioblasts Cell Stem Cell 2020 27 254 269 10.1016/j.stem.2020.06.007 32640183 · DOI
  174. [179]Edge S.B. Hoeg J.M. Triche T. Schneider P.D. Brewer H.B. Jr. Cultured human hepatocytes. Evidence for metabolism of low density lipoproteins by a pathway independent of the classical low density lipoprotein receptor J. Biol. Chem. 1986 261 3800 3806 10.1016/S0021-9258(17)35718-6 3949791 · DOI
  175. [180]Ose L. Ose T. Norum K.R. Berg T. Uptake and degradation of 125I-labelled high density lipoproteins in rat liver cells in vivo and in vitro Biochim. Biophys. Acta Lipids Lipid Metab. 1979 574 521 536 10.1016/0005-2760(79)90248-0 226159 · DOI
  176. [181]Silver D.L. Wang N. Tall A.R. Defective HDL particle uptake in ob/ob hepatocytes causes decreased recycling, degradation, and selective lipid uptake J. Clin. Investig. 2000 105 151 159 10.1172/JCI8087 10642593 PMC377432 · DOI
  177. [182]Mee C.J. Harris H.J. Farquhar M.J. Wilson G. Reynolds G. Davis C. van IJzendoorn I.S.C. Balfe P. McKeating J.A. Polarization restricts hepatitis C virus entry into HepG2 hepatoma cells J. Virol. 2009 83 6211 6221 10.1128/JVI.00246-09 19357163 PMC2687400 · DOI
  178. [183]Ramos M.J. Bandiera L. Menolascina F. Fallowfield J.A. In vitro models for non-alcoholic fatty liver disease: Emerging platforms and their applications iScience 2022 25 103549 10.1016/j.isci.2021.103549 34977507 PMC8689151 · DOI · Paper page
  179. [184]Borén J. Wettesten M. Sjöberg A. Thorlin T. Bondjers G. Wiklund O. Olofsson S.O. The assembly and secretion of apoB 100 containing lipoproteins in Hep G2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly J. Biol. Chem. 1990 265 10556 10564 10.1016/S0021-9258(18)86983-6 2162354 · DOI
  180. [185]Ellsworth J.L. Erickson S.K. Cooper A.D. Very low and low density lipoprotein synthesis and secretion by the human hepatoma cell line Hep-G2: Effects of free fatty acid J. Lipid Res. 1986 27 858 874 10.1016/S0022-2275(20)38780-0 3021884 · DOI
  181. [186]Dashti N. Wolfbauer G. Secretion of lipids, apolipoproteins, and lipoproteins by human hepatoma cell line, HepG2: Effects of oleic acid and insulin J. Lipid Res. 1987 28 423 436 10.1016/S0022-2275(20)38686-7 3035039 · DOI
  182. [187]Gibbons G.F. Khurana R. Odwell A. Seelaender M.C. Lipid balance in HepG2 cells: Active synthesis and impaired mobilization J. Lipid Res. 1994 35 1801 1808 10.1016/S0022-2275(20)39775-3 7852857 · DOI
  183. [188]Hugo-Wissemann D. Anundi I. Lauchart W. Viebahn R. de Groot H. Differences in glycolytic capacity and hypoxia tolerance between hepatoma cells and hepatocytes Hepatology 1991 13 297 303 10.1002/hep.1840130215 1847350 · DOI
  184. [189]Javitt N.B. Hep G2 cells as a resource for metabolic studies: Lipoprotein, cholesterol, and bile acids Faseb J 1990 4 161 168 10.1096/fasebj.4.2.2153592 2153592 · DOI
  185. [190]Mavri-Damelin D. Damelin L.H. Eaton S. Rees M. Selden C. Hodgson H.J.F. Cells for bioartificial liver devices: The human hepatoma-derived cell line C3A produces urea but does not detoxify ammonia Biotechnol. Bioeng. 2008 99 644 651 10.1002/bit.21599 17680661 · DOI
  186. [191]Iyer V.V. Yang H. Ierapetritou M.G. Roth C.M. Effects of glucose and insulin on HepG2-C3A cell metabolism Biotechnol. Bioeng. 2010 107 347 356 10.1002/bit.22799 20506178 · DOI
  187. [192]Larsen L.E. Smith M.A. Abbey D. Korn A. Reeskamp L.F. Hand N.J. Holleboom A.G. Hepatocyte-like cells derived from induced pluripotent stem cells: A versatile tool to understand lipid disorders Atherosclerosis 2020 303 8 14 10.1016/j.atherosclerosis.2020.03.014 32460140 · DOI
  188. [193]Robinson J.F. Hamilton E.G. Lam J. Chen H. Woodruff T.J. Differences in cytochrome p450 enzyme expression and activity in fetal and adult tissues Placenta 2020 100 35 44 10.1016/j.placenta.2020.07.009 32818874 PMC8021394 · DOI · Paper page
  189. [194]Kido T. Koui Y. Suzuki K. Kobayashi A. Miura Y. Chern E.Y. Tanaka M. Miyajima A. CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells Stem Cell Rep. 2015 5 508 515 10.1016/j.stemcr.2015.08.008 26365514 PMC4624956 · DOI
  190. [195]Sato K. Zhang W. Safarikia S. Isidan A. Chen A.M. Li P. Francis H. Kennedy L. Baiocchi L. Alvaro D. Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma Hepatology 2021 74 491 502 10.1002/hep.31653 33222247 PMC8529583 · DOI
  191. [197]de Graaf I.A. Olinga P. de Jager M.H. Merema M.T. de Kanter R. van de Kerkhof E.G. Groothuis G.M. Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies Nat. Protoc. 2010 5 1540 1551 10.1038/nprot.2010.111 20725069 · DOI
  192. [198]van Swelm R.P. Hadi M. Laarakkers C.M. Masereeuw R. Groothuis G.M. Russel F.G. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury J. Appl. Toxicol. 2014 34 993 1001 10.1002/jat.2917 24038040 · DOI
  193. [199]Konsue N. Ioannides C. Modulation of carcinogen-metabolising cytochromes P450 in human liver by the chemopreventive phytochemical phenethyl isothiocyanate, a constituent of cruciferous vegetables Toxicology 2010 268 184 190 10.1016/j.tox.2009.12.011 20025923 · DOI
  194. [200]van de Bovenkamp M. Groothuis G.M. Meijer D.K. Olinga P. Liver slices as a model to study fibrogenesis and test the effects of anti-fibrotic drugs on fibrogenic cells in human liver Toxicol Vitr. 2008 22 771 778 10.1016/j.tiv.2007.11.019 18207697 · DOI
  195. [201]Wang Y. Leaker B. Qiao G. Sojoodi M. Eissa I.R. Epstein E.T. Eddy J. Dimowo O. Lauer G.M. Qadan M. Precision-cut liver slices as an ex vivo model to evaluate antifibrotic therapies for liver fibrosis and cirrhosis Hepatol. Commun. 2024 8 e0558 10.1097/HC9.0000000000000558 39445861 PMC11512631 · DOI
  196. [202]Palma E. Doornebal E.J. Chokshi S. Precision-cut liver slices: A versatile tool to advance liver research Hepatol. Int. 2019 13 51 57 10.1007/s12072-018-9913-7 30515676 PMC6513823 · DOI · Paper page
  197. [203]Li M. Larsen F.T. van den Heuvel M.C. Gier K. Gorter A.R. Oosterhuis D. Bijzet J. de Meijer V.E. Ravnskjaer K. Nagelkerke A. Metabolic Dysfunction-Associated Steatotic Liver Disease in a Dish: Human Precision-Cut Liver Slices as a Platform for Drug Screening and Interventions Nutrients 2024 16 626 10.3390/nu16050626 38474754 PMC10934612 · DOI
  198. [204]Hammoutene A. Laouirem S. Albuquerque M. Colnot N. Brzustowski A. Valla D. Provost N. Delerive P. Paradis V. A new NRF2 activator for the treatment of human metabolic dysfunction-associated fatty liver disease JHEP Rep. 2023 5 100845 10.1016/j.jhepr.2023.100845 37663119 PMC10472315 · DOI
  199. [205]van Midwoud P.M. Merema M.T. Verpoorte E. Groothuis G.M. Microfluidics enables small-scale tissue-based drug metabolism studies with scarce human tissue J. Lab. Autom. 2011 16 468 476 10.1016/j.jala.2011.07.003 22093304 · DOI
  200. [206]Vickers A.E. Saulnier M. Cruz E. Merema M.T. Rose K. Bentley P. Olinga P. Organ slice viability extended for pathway characterization: An in vitro model to investigate fibrosis Toxicol. Sci. 2004 82 534 544 10.1093/toxsci/kfh285 15456927 · DOI

200 of 241 shown

Authors
Kiss, I., Neuwert, N., Oberle, R., Hengstschläger, M., Osmanagic-Myers, S., & Stangl, H.
Affiliations
  • Medical University of Vienna (AT)
  • Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University Vienna, Vienna 1090, Austria
Corresponding author
Stangl, Herbert
ORCID
Venue
Biomolecules
Publisher
MDPI AG
Published
2025-07-02
Volume
15
Issue
7
Pages
956
ISSN
2218-273X (ISSN-L)
DOI
10.3390/biom15070956
PMC
PMC12292278
OpenAlex
W4411961046
Cited by
11
References
252
Citations by year
2026: 9 · 2025: 2
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomolecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Austrian Science Fund (P 37003, Austrian Science Fund)
  • 10.55776/PAT1364323 (P 37003, Austrian Science Fund)
  • The Margaretha Hehberger-Cancer Research Fund (P 37003, Austrian Science Fund)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
hepatic lipoprotein metabolism, lipoprotein uptake, lipoprotein secretion, in vitro liver models, liver spheroids, precision-cut liver slices, liver-on-a-chip, induced pluripotent stem cells, embryonic stem cells, familial hypercholesterolemia, non-alcoholic fatty liver disease, metabolic syndrome, atherosclerosis, primary human hepatocytes
MeSH terms
Animals, Humans, Lipoproteins, Liver, Hepatocytes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review