CoChat
Sign Up
Cited by 538Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthCancer, Lipids, and Metabolism

Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics

Open access
Duan, Yajun, Gong, Ke, Xu, Suowen, Zhang, Feng, Meng, Xianshe, Han, Jihong·2022·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-022-01125-5PMC PMC9344793
Open this paper in CoChat — free accountOpen PDF

Abstract

Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. More and more studies have shown that lowering cholesterol level, especially low-density lipoprotein cholesterol level, protects cardiovascular system and prevents cardiovascular events effectively. Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion. Herein, we summarize the historical review and research events, the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis, and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances. More importantly, we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.

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 · 10.1038/s41392-022-01125-5

Cites

58 of 58 references verified0 citation errors · 0 not checkable

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?

  • Intracellular cholesterol accumulation provides a potential explanation for the reduced nuclear localization of Srebp2 in Mecp2 KO astrocytes, given negative feedback.

    “Notably, the accumulation of intracellular cholesterol provides a potential explanation for the reduced nuclear localization of Srebp2 observed in KO astrocytes, given the negative feedback exerted by intracellular cholesterol on Srebp2 activation (Duan et al., 2022;N.-Q. Wang et al., 2025).”

    From Impaired astrocyte-to-neuron cholesterol trafficking drives synaptic dysfunction in Rett syndrome (2026) · cites this paper as Duan et al., 2022

  • Intracellular cholesterol inhibits Srebp2 activation through a negative feedback mechanism.

    “However, intracellular cholesterol is known to inhibit Srebp2 activation through a negative feedback mechanism (Duan et al., 2022;Wang et al., 2025).”

    From Impaired astrocyte-to-neuron cholesterol trafficking drives synaptic dysfunction in Rett syndrome (2026) · cites this paper as Duan et al., 2022

Self-check

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

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

Cites

Flagged first, then by citations

Research works printed but not linked: 526

  1. [1]Vance DE Van den Bosch H Cholesterol in the year 2000 Biochim. Biophys. Acta 2000 1529 1 8 10.1016/S1388-1981(00)00133-5 11111073 · DOI
  2. [2]Nicholls M Adolf otto reinhold windaus Eur. Heart J. 2019 40 2659 2660 10.1093/eurheartj/ehz573 31433847 · DOI
  3. [3]Kennedy EP Westheimer FH Nobel laureates: Bloch and Lynen win prize in medicine and physiology Science 1964 146 504 506 10.1126/science.146.3643.504 17806799 · DOI
  4. [4]Brown MS Goldstein JL Cholesterol feedback: from Schoenheimer’s bottle to Scap’s MELADL J. Lipid Res. 2009 50 S15 S27 10.1194/jlr.R800054-JLR200 18974038 PMC2674699 · DOI
  5. [5]Schoenheimer R Breusch F Synthesis and destruction of cholesterol in the organism J. Biol. Chem. 1933 103 439 448 10.1016/S0021-9258(18)75823-7 · DOI
  6. [6]Brown MS Goldstein JL The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor Cell 1997 89 331 340 10.1016/S0092-8674(00)80213-5 9150132 · DOI · Paper page
  7. [7]Brown MS Ye J Rawson RB Goldstein JL Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans Cell 2000 100 391 398 10.1016/S0092-8674(00)80675-3 10693756 · DOI · Paper page
  8. [9]Endo A A historical perspective on the discovery of statins Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 2010 86 484 493 10.2183/pjab.86.484 20467214 PMC3108295 · DOI
  9. [11]Lee YT Mouse models of atherosclerosis: a historical perspective and recent advances Lipids Health Dis. 2017 16 12 10.1186/s12944-016-0402-5 28095860 PMC5240327 · DOI
  10. [13]Grebe A Latz E Cholesterol crystals and inflammation Curr. Rheumatol. Rep. 2013 15 313 10.1007/s11926-012-0313-z 23412688 PMC3623938 · DOI
  11. [14]Baumer Y Mehta NN Dey AK Powell-Wiley TM Boisvert WA Cholesterol crystals and atherosclerosis Eur. Heart J. 2020 41 2236 2239 10.1093/eurheartj/ehaa505 32572475 PMC7850045 · DOI
  12. [17]Janoudi A Shamoun FE Kalavakunta JK Abela GS Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque Eur. Heart J. 2016 37 1959 1967 10.1093/eurheartj/ehv653 26705388 · DOI
  13. [18]Soehnlein O Libby P Targeting inflammation in atherosclerosis—from experimental insights to the clinic Nat. Rev. Drug Discov. 2021 20 589 610 10.1038/s41573-021-00198-1 33976384 PMC8112476 · DOI
  14. [20]Gofman JW Lindgren FT Elliott H Ultracentrifugal studies of lipoproteins of human serum J. Biol. Chem. 1949 179 973 979 10.1016/S0021-9258(19)51290-X 18150027 · DOI
  15. [21]Gofman JW Lindgren F The role of lipids and lipoproteins in atherosclerosis Science 1950 111 166 171 10.1126/science.111.2877.166 15403115 · DOI
  16. [22]Gofman JW Serum lipoproteins and the evaluation of atherosclerosis Ann. N. Y. Acad. Sci. 1956 64 590 595 10.1111/j.1749-6632.1956.tb36833.x 13373230 · DOI
  17. [23]Castelli WP Anderson K Wilson PW Levy D Lipids and risk of coronary heart disease framingham study Ann. Epidemiol. 1992 2 23 28 10.1016/1047-2797(92)90033-M 1342260 · DOI
  18. [25]Khachadurian AK The inheritance of essential familial hypercholesterolemia Am. J. Med. 1964 37 402 407 10.1016/0002-9343(64)90196-2 14209286 · DOI
  19. [26]Steinberg D Thematic review series: The pathogenesis of atherosclerosis: an interpretive history of the cholesterol controversy, part III: Mechanistically defining the role of hyperlipidemia J. Lipid Res. 2005 46 2037 2051 10.1194/jlr.R500010-JLR200 15995167 · DOI
  20. [29]Endo A Kuroda M Tanzawa K Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity FEBS Lett. 1976 72 323 326 10.1016/0014-5793(76)80996-9 16386050 · DOI
  21. [30]Brown MS Faust JR Goldstein JL Kaneko I Endo A Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase J. Biol. Chem. 1978 253 1121 1128 10.1016/S0021-9258(17)38120-6 624722 · DOI
  22. [31]Cho L A practical approach to the cholesterol guidelines and ASCVD prevention Cleve Clin. J. Med. 2020 87 15 20 10.3949/ccjm.87.s1.02 32349970 · DOI
  23. [32]Davidson MH Efficacy of simvastatin and ezetimibe in treating hypercholesterolemia J. Am. Coll. Cardiol. 2003 42 398 399 10.1016/S0735-1097(03)00638-7 12875794 · DOI
  24. [33]Seidah NG The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation Proc. Natl Acad. Sci. USA 2003 100 928 933 10.1073/pnas.0335507100 12552133 PMC298703 · DOI · Paper page
  25. [34]Lagace TA Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice J. Clin. Investig. 2006 116 2995 3005 10.1172/JCI29383 17080197 PMC1626117 · DOI · Paper page
  26. [35]Zhang DW Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation J. Biol. Chem. 2007 282 18602 18612 10.1074/jbc.M702027200 17452316 · DOI · Paper page
  27. [36]Kim EJ Wierzbicki AS The history of proprotein convertase subtilisin kexin-9 inhibitors and their role in the treatment of cardiovascular disease Ther. Adv. Chronic Dis. 2020 11 2040622320924569 10.1177/2040622320924569 32537117 PMC7268157 · DOI
  28. [37]Lamb YN Inclisiran: first approval Drugs 2021 81 389 395 10.1007/s40265-021-01473-6 33620677 PMC7900795 · DOI
  29. [38]Sanjay KV ATP citrate lyase inhibitor Bempedoic acid alleviate long term HFD induced NASH through improvement in glycemic control, reduction of hepatic triglycerides & total cholesterol, modulation of inflammatory & fibrotic genes and improvement in NAS score Curr. Res Pharm. Drug Discov. 2021 2 100051 10.1016/j.crphar.2021.100051 PMC8663992 34909677 · DOI
  30. [39]Govindaraju A Sabarathinam S Bempedoic acid: a nonstatin drug for the management of hypercholesterolemia Health Sci. Rep. 2021 4 e431 10.1002/hsr2.431 34786488 PMC8577242 · DOI
  31. [40]Feng X Zhang L Xu S Shen AZ ATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: an updated review Prog. Lipid Res. 2020 77 101006 10.1016/j.plipres.2019.101006 31499095 · DOI
  32. [41]Kapourchali FR Surendiran G Goulet A Moghadasian MH The role of dietary cholesterol in lipoprotein metabolism and related metabolic abnormalities: a mini-review Crit. Rev. Food Sci. Nutr. 2016 56 2408 2415 10.1080/10408398.2013.842887 26055276 · DOI
  33. [42]Rosenson RS Song WL Egg yolk, source of bad cholesterol and good lipids? Am. J. Clin. Nutr. 2019 110 548 549 10.1093/ajcn/nqz105 31172168 PMC6895541 · DOI
  34. [44]Iqbal J Hussain MM Intestinal lipid absorption Am. J. Physiol. Endocrinol. Metab. 2009 296 E1183 E1194 10.1152/ajpendo.90899.2008 19158321 PMC2692399 · DOI · Paper page
  35. [45]Altmann SW Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption Science 2004 303 1201 1204 10.1126/science.1093131 14976318 · DOI
  36. [46]Fumeron F Bard JM Lecerf JM Interindividual variability in the cholesterol-lowering effect of supplementation with plant sterols or stanols Nutr. Rev. 2017 75 134 145 10.1093/nutrit/nuw059 28158760 · DOI
  37. [47]Cusack LK Fernandez ML Volek JS The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol Adv. Nutr. 2013 4 633 643 10.3945/an.113.004507 24228192 PMC3823509 · DOI
  38. [48]Huff MW Pollex RL Hegele RA NPC1L1: evolution from pharmacological target to physiological sterol transporter Arterioscler. Thromb. Vasc. Biol. 2006 26 2433 2438 10.1161/01.ATV.0000245791.53245.ee 16973966 · DOI
  39. [49]Dietschy JM Gamel WG Cholesterol synthesis in the intestine of man: regional differences and control mechanisms J. Clin. Investig. 1971 50 872 880 10.1172/JCI106559 4993859 PMC292002 · DOI
  40. [50]Nestel PJ Poyser A Changes in cholesterol synthesis and excretion when cholesterol intake is increased Metabolism 1976 25 1591 1599 10.1016/0026-0495(76)90112-8 1036602 · DOI
  41. [51]Rudney H Sexton RC Regulation of cholesterol biosynthesis Annu. Rev. Nutr. 1986 6 245 272 10.1146/annurev.nu.06.070186.001333 3524618 · DOI
  42. [52]Bloch K The biological synthesis of cholesterol Science 1965 150 19 28 10.1126/science.150.3692.19 5319508 · DOI
  43. [54]DeBose-Boyd RA Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase Cell Res 2008 18 609 621 10.1038/cr.2008.61 18504457 PMC2742364 · DOI · Paper page
  44. [55]Yokoyama C SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene Cell 1993 75 187 197 10.1016/S0092-8674(05)80095-9 8402897 · DOI
  45. [56]Gong X Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization Cell Res 2016 26 1197 1211 10.1038/cr.2016.123 27811944 PMC5099872 · DOI
  46. [57]Brown MS Radhakrishnan A Goldstein JL Retrospective on cholesterol homeostasis: the central role of SCAP Annu. Rev. Biochem. 2018 87 783 807 10.1146/annurev-biochem-062917-011852 28841344 PMC5828883 · DOI
  47. [58]Luo J Yang H Song BL Mechanisms and regulation of cholesterol homeostasis Nat. Rev. Mol. Cell Biol. 2020 21 225 245 10.1038/s41580-019-0190-7 31848472 · DOI · Paper page
  48. [59]Kober DL SCAP structures highlight key role for rotation of intertwined luminal loops in cholesterol sensing Cell 2021 184 3689 3701 e3622 10.1016/j.cell.2021.05.019 34139175 PMC8277531 · DOI
  49. [60]Yan R A structure of human SCAP bound to INSIG-2 suggests how their interaction is regulated by sterols Science 2021 371 eabb2224 10.1126/science.abb2224 33446483 · DOI · Paper page
  50. [61]Sharpe LJ Coates HW Brown AJ Post-translational control of the long and winding road to cholesterol J. Biol. Chem. 2020 295 17549 17559 10.1074/jbc.REV120.010723 33453997 PMC7762936 · DOI
  51. [62]Luskey KL Stevens B Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation J. Biol. Chem. 1985 260 10271 10277 10.1016/S0021-9258(17)39242-6 2991281 · DOI
  52. [63]Song BL Sever N DeBose-Boyd RA Gp78, a membrane-anchored ubiquitin ligase, associates with INSIG-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase Mol. Cell 2005 19 829 840 10.1016/j.molcel.2005.08.009 16168377 · DOI
  53. [64]Cao J Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase Cell Metab. 2007 6 115 128 10.1016/j.cmet.2007.07.002 17681147 · DOI
  54. [65]Lee JN Song B DeBose-Boyd RA Ye J Sterol-regulated degradation of INSIG-1 mediated by the membrane-bound ubiquitin ligase gp78 J. Biol. Chem. 2006 281 39308 39315 10.1074/jbc.M608999200 17043353 · DOI
  55. [66]Liu TF Ablation of gp78 in liver improves hyperlipidemia and insulin resistance by inhibiting SREBP to decrease lipid biosynthesis Cell Metab. 2012 16 213 225 10.1016/j.cmet.2012.06.014 22863805 · DOI
  56. [67]Lu XY Feeding induces cholesterol biosynthesis via the mTORC1-USP20-HMGCR axis Nature 2020 588 479 484 10.1038/s41586-020-2928-y 33177714 · DOI
  57. [68]Clarke PR Hardie DG Regulation of HMG-CoA reductase: Identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver EMBO J. 1990 9 2439 2446 10.1002/j.1460-2075.1990.tb07420.x 2369897 PMC552270 · DOI
  58. [69]Sato R Goldstein JL Brown MS Replacement of serine-871 of hamster 3-hydroxy-3-methylglutaryl-CoA reductase prevents phosphorylation by AMP-activated kinase and blocks inhibition of sterol synthesis induced by ATP depletion Proc. Natl Acad. Sci. USA 1993 90 9261 9265 10.1073/pnas.90.20.9261 8415689 PMC47547 · DOI
  59. [70]min HK Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease Cell Metab. 2012 15 665 674 10.1016/j.cmet.2012.04.004 22560219 PMC3361911 · DOI
  60. [71]Zhang X Thyroid-stimulating hormone decreases HMG-CoA reductase phosphorylation via AMP-activated protein kinase in the liver J. Lipid Res. 2015 56 963 971 10.1194/jlr.M047654 25713102 PMC4409286 · DOI
  61. [72]Rosenson RS Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport Circulation 2012 125 1905 1919 10.1161/CIRCULATIONAHA.111.066589 22508840 PMC4159082 · DOI · Paper page
  62. [73]van der Velde AE Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice Gastroenterology 2007 133 967 975 10.1053/j.gastro.2007.06.019 17854600 · DOI
  63. [74]Schwartz CC Vlahcevic ZR Halloran LG Swell L An in vivo evaluation in man of the transfer of esterified cholesterol between lipoproteins and into the liver and bile Biochim. Biophys. Acta 1981 663 143 162 10.1016/0005-2760(81)90201-0 7011409 · DOI
  64. [75]Brandts J Ray KK Familial hypercholesterolemia: JACC focus seminar 4/4 J. Am. Coll. Cardiol. 2021 78 1831 1843 10.1016/j.jacc.2021.09.004 34711342 · DOI
  65. [76]Yu L Cholesterol-regulated translocation of NPC1L1 to the cell surface facilitates free cholesterol uptake J. Biol. Chem. 2006 281 6616 6624 10.1074/jbc.M511123200 16407187 · DOI
  66. [77]Wang J Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption J. Lipid Res. 2009 50 1653 1662 10.1194/jlr.M800669-JLR200 19325169 PMC2724045 · DOI
  67. [78]Infante RE Purified NPC1L1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop J. Biol. Chem. 2008 283 1064 1075 10.1074/jbc.M707944200 17989072 · DOI
  68. [79]Xie C Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine J. Lipid Res. 2012 53 2092 2101 10.1194/jlr.M027359 22811412 PMC3435542 · DOI
  69. [80]Li PS The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1 Nat. Med. 2014 20 80 86 10.1038/nm.3417 24336247 · DOI
  70. [81]Johnson TA Pfeffer SR Ezetimibe-sensitive cholesterol uptake by NPC1L1 protein does not require endocytosis Mol. Biol. Cell 2016 27 1845 1852 10.1091/mbc.e16-03-0154 27075173 PMC4884074 · DOI
  71. [82]Huang CS Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition Sci. Adv. 2020 6 eabb1989 10.1126/sciadv.abb1989 32596471 PMC7304964 · DOI
  72. [83]Hu M Structural insights into the mechanism of human NPC1L1-mediated cholesterol uptake Sci. Adv. 2021 7 eabg3188 10.1126/sciadv.abg3188 34272236 PMC8284890 · DOI
  73. [84]Long T Liu Y Qin Y DeBose-Boyd RA Li X Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption Sci. Adv. 2021 7 eabh3997 10.1126/sciadv.abh3997 34407950 PMC8373123 · DOI
  74. [85]Clader JW The discovery of ezetimibe: a view from outside the receptor J. Med. Chem. 2004 47 1 9 10.1021/jm030283g 14695813 · DOI
  75. [86]Zhang R Niemann-Pick C1-Like 1 inhibitors for reducing cholesterol absorption Eur. J. Med. Chem. 2022 230 114111 10.1016/j.ejmech.2022.114111 35063734 · DOI
  76. [87]Jia L Betters JL Yu L Niemann-Pick C1-Like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport Annu. Rev. Physiol. 2011 73 239 259 10.1146/annurev-physiol-012110-142233 20809793 PMC3965667 · DOI
  77. [88]Yan J Horng T Lipid metabolism in regulation of macrophage functions Trends Cell Biol. 2020 30 979 989 10.1016/j.tcb.2020.09.006 33036870 · DOI
  78. [89]Chistiakov DA Melnichenko AA Myasoedova VA Grechko AV Orekhov AN Mechanisms of foam cell formation in atherosclerosis J. Mol. Med. 2017 95 1153 1165 10.1007/s00109-017-1575-8 28785870 · DOI
  79. [90]Dandan M Turnover rates of the low-density lipoprotein receptor and PCSK9: added dimension to the cholesterol homeostasis model Arterioscler Thromb. Vasc. Biol. 2021 41 2866 2876 10.1161/ATVBAHA.121.316764 34615375 · DOI
  80. [92]Kzhyshkowska J Neyen C Gordon S Role of macrophage scavenger receptors in atherosclerosis Immunobiology 2012 217 492 502 10.1016/j.imbio.2012.02.015 22437077 · DOI
  81. [93]Kunjathoor VV Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages J. Biol. Chem. 2002 277 49982 49988 10.1074/jbc.M209649200 12376530 · DOI
  82. [94]Wang D Targeting foam cell formation in atherosclerosis: therapeutic potential of natural products Pharm. Rev. 2019 71 596 670 10.1124/pr.118.017178 31554644 · DOI
  83. [95]Moore KJ Sheedy FJ Fisher EA Macrophages in atherosclerosis: a dynamic balance Nat. Rev. Immunol. 2013 13 709 721 10.1038/nri3520 23995626 PMC4357520 · DOI · Paper page
  84. [96]Melton EM Myeloid Acat1/Soat1 KO attenuates pro-inflammatory responses in macrophages and protects against atherosclerosis in a model of advanced lesions J. Biol. Chem. 2019 294 15836 15849 10.1074/jbc.RA119.010564 31495784 PMC6816086 · DOI
  85. [97]Huang LH Myeloid Acyl-CoA: cholesterol acyltransferase 1 deficiency reduces lesion macrophage content and suppresses atherosclerosis progression J. Biol. Chem. 2016 291 6232 6244 10.1074/jbc.M116.713818 26801614 PMC4813549 · DOI
  86. [98]Shao D Grape seed proanthocyanidins suppressed macrophage foam cell formation by miRNA-9 via targeting ACAT1 in THP-1 cells Food Funct. 2020 11 1258 1269 10.1039/C9FO02352F 31967154 · DOI
  87. [99]Wang B He PP Zeng GF Zhang T Ou Yang XP miR-467b regulates the cholesterol ester formation via targeting ACAT1 gene in RAW 264.7 macrophages Biochimie 2017 132 38 44 10.1016/j.biochi.2016.09.012 27678191 · DOI
  88. [100]Meuwese MC ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial JAMA 2009 301 1131 1139 10.1001/jama.301.11.1131 19293413 · DOI
  89. [101]Tardif JC Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions Circulation 2004 110 3372 3377 10.1161/01.CIR.0000147777.12010.EF 15533865 · DOI
  90. [102]Warner GJ Stoudt G Bamberger M Johnson WJ Rothblat GH Cell toxicity induced by inhibition of acyl coenzyme A: cholesterol acyltransferase and accumulation of unesterified cholesterol J. Biol. Chem. 1995 270 5772 5778 10.1074/jbc.270.11.5772 7890706 · DOI
  91. [103]Ouimet M Marcel YL Regulation of lipid droplet cholesterol efflux from macrophage foam cells Arterioscler. Thromb. Vasc. Biol. 2012 32 575 581 10.1161/ATVBAHA.111.240705 22207731 · DOI
  92. [104]Zhao B Song JSt Clair RW Ghosh S Stable overexpression of human macrophage cholesteryl ester hydrolase results in enhanced free cholesterol efflux from human THP1 macrophages Am. J. Physiol. Cell Physiol. 2007 292 C405 C412 10.1152/ajpcell.00306.2006 16971496 · DOI
  93. [105]Sekiya M Ablation of neutral cholesterol ester hydrolase 1 accelerates atherosclerosis Cell Metab. 2009 10 219 228 10.1016/j.cmet.2009.08.004 19723498 · DOI
  94. [106]Favari E Cholesterol efflux and reverse cholesterol transport Handb. Exp. Pharm. 2015 224 181 206 10.1007/978-3-319-09665-0_4 25522988 · DOI
  95. [107]Adorni MP The roles of different pathways in the release of cholesterol from macrophages J. Lipid Res. 2007 48 2453 2462 10.1194/jlr.M700274-JLR200 17761631 · DOI
  96. [108]Yancey PG Importance of different pathways of cellular cholesterol efflux Arterioscler. Thromb. Vasc. Biol. 2003 23 712 719 10.1161/01.ATV.0000057572.97137.DD 12615688 · DOI
  97. [109]Anastasius M Cholesterol efflux capacity: an introduction for clinicians Am. Heart J. 2016 180 54 63 10.1016/j.ahj.2016.07.005 27659883 · DOI
  98. [110]Qian H Structure of the human lipid exporter ABCA1 Cell 2017 169 1228 1239 e1210 10.1016/j.cell.2017.05.020 28602350 · DOI
  99. [111]Wang N Lan D Chen W Matsuura F Tall AR ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins Proc. Natl Acad. Sci. USA 2004 101 9774 9779 10.1073/pnas.0403506101 15210959 PMC470750 · DOI
  100. [112]Out R Combined deletion of macrophage ABCA1 and ABCG1 leads to massive lipid accumulation in tissue macrophages and distinct atherosclerosis at relatively low plasma cholesterol levels Arterioscler. Thromb. Vasc. Biol. 2008 28 258 264 10.1161/ATVBAHA.107.156935 18006857 · DOI
  101. [113]Costet P Luo Y Wang N Tall AR Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor J. Biol. Chem. 2000 275 28240 28245 10.1074/jbc.M003337200 10858438 · DOI
  102. [114]Shen WJ Azhar S Kraemer FB SR-BI: A unique multifunctional receptor for cholesterol influx and efflux Annu. Rev. Physiol. 2018 80 95 116 10.1146/annurev-physiol-021317-121550 29125794 PMC6376870 · DOI
  103. [115]Lim HY Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-mediated transport of HDL Cell Metab. 2013 17 671 684 10.1016/j.cmet.2013.04.002 23663736 · DOI
  104. [116]Phillips MC Molecular mechanisms of cellular cholesterol efflux J. Biol. Chem. 2014 289 24020 24029 10.1074/jbc.R114.583658 25074931 PMC4148835 · DOI
  105. [117]De Lalla OF Gofman JW Ultracentrifugal analysis of serum lipoproteins Methods Biochem. Anal. 1954 1 459 478 13193538
  106. [118]Kontush A Structure of HDL: particle subclasses and molecular components Handb. Exp. Pharm. 2015 224 3 51 10.1007/978-3-319-09665-0_1 25522985 · DOI
  107. [119]Marques LR Reverse cholesterol transport: molecular mechanisms and the non-medical approach to enhance HDL cholesterol Front. Physiol. 2018 9 526 10.3389/fphys.2018.00526 29867567 PMC5962737 · DOI
  108. [120]Glickman RM Green PH Lees RS Tall A Apoprotein A-I synthesis in normal intestinal mucosa and in Tangier disease N. Engl. J. Med. 1978 299 1424 1427 10.1056/NEJM197812282992602 213720 · DOI
  109. [121]Dieplinger H Zechner R Kostner GM The in vitro formation of HDL2 during the action of LCAT: The role of triglyceride-rich lipoproteins J. Lipid Res. 1985 26 273 282 10.1016/S0022-2275(20)34369-8 3989387 · DOI
  110. [122]Vaughan AM Oram JF ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins J. Biol. Chem. 2005 280 30150 30157 10.1074/jbc.M505368200 15994327 · DOI
  111. [123]Ji Y Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux J. Biol. Chem. 1997 272 20982 20985 10.1074/jbc.272.34.20982 9261096 · DOI
  112. [124]Fielding CJ Shore VG Fielding PE A protein cofactor of lecithin: cholesterol acyltransferase Biochem. Biophys. Res. Commun. 1972 46 1493 1498 10.1016/0006-291X(72)90776-0 4335615 · DOI
  113. [125]Jonas A Lecithin-cholesterol acyltransferase in the metabolism of high-density lipoproteins Biochim. Biophys. Acta 1991 1084 205 220 10.1016/0005-2760(91)90062-M 1888769 · DOI
  114. [126]Bruce C Beamer LJ Tall AR The implications of the structure of the bactericidal/permeability-increasing protein on the lipid-transfer function of the cholesteryl ester transfer protein Curr. Opin. Struct. Biol. 1998 8 426 434 10.1016/S0959-440X(98)80118-8 9729732 · DOI
  115. [128]Davidson MH HDL and CETP inhibition: will this define the future? Curr. Treat. Options Cardiovasc. Med. 2012 14 384 390 10.1007/s11936-012-0191-8 22723175 · DOI
  116. [129]Furtado JD Pharmacological inhibition of CETP (cholesteryl ester transfer protein) increases HDL (high-density lipoprotein) that contains APOC3 and other HDL subspecies associated with higher risk of coronary heart disease Arterioscler. Thromb. Vasc. Biol. 2022 42 227 237 10.1161/ATVBAHA.121.317181 34937388 PMC8785774 · DOI
  117. [130]Rousset X Shamburek R Vaisman B Amar M Remaley AT Lecithin cholesterol acyltransferase: an anti- or pro-atherogenic factor? Curr. Atheroscler. Rep. 2011 13 249 256 10.1007/s11883-011-0171-6 21331766 PMC3794709 · DOI
  118. [131]Pownall HJ Rosales C Gillard BK Gotto AM Jr High-density lipoproteins, reverse cholesterol transport and atherogenesis Nat. Rev. Cardiol. 2021 18 712 723 10.1038/s41569-021-00538-z 33833449 · DOI
  119. [133]Hamer M O’Donovan G Stamatakis E High-density lipoprotein cholesterol and mortality: too much of a good thing? Arterioscler. Thromb. Vasc. Biol. 2018 38 669 672 10.1161/ATVBAHA.117.310587 29326314 · DOI
  120. [134]Nordestgaard BG Tybjaerg-Hansen A IDL, VLDL, chylomicrons and atherosclerosis Eur. J. Epidemiol. 1992 8 92 98 10.1007/BF00145358 1505659 · DOI
  121. [135]Barter PJ Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis Arterioscler. Thromb. Vasc. Biol. 2003 23 160 167 10.1161/01.ATV.0000054658.91146.64 12588754 · DOI
  122. [136]Brown MS Goldstein JL How LDL receptors influence cholesterol and atherosclerosis Sci. Am. 1984 251 58 66 10.1038/scientificamerican1184-58 6390676 · DOI
  123. [137]Shu H A novel indel variant in LDLR responsible for familial hypercholesterolemia in a Chinese family PLoS One 2017 12 e0189316 10.1371/journal.pone.0189316 29228028 PMC5724832 · DOI
  124. [138]Jiang L Analysis of LDLR variants from homozygous FH patients carrying multiple mutations in the LDLR gene Atherosclerosis 2017 263 163 170 10.1016/j.atherosclerosis.2017.06.014 28645073 · DOI
  125. [139]Calkin AC FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors Proc. Natl Acad. Sci. USA 2011 108 20107 20112 10.1073/pnas.1111589108 22109552 PMC3250164 · DOI · Paper page
  126. [140]Wang JK Ablation of plasma prekallikrein decreases low-density lipoprotein cholesterol by stabilizing low-density lipoprotein receptor and protects against atherosclerosis Circulation 2022 145 675 687 10.1161/CIRCULATIONAHA.121.056491 35189703 · DOI
  127. [141]Liscum L Underwood KW Intracellular cholesterol transport and compartmentation J. Biol. Chem. 1995 270 15443 15446 10.1074/jbc.270.26.15443 7797533 · DOI
  128. [142]Simons K Ikonen E How cells handle cholesterol Science 2000 290 1721 1726 10.1126/science.290.5497.1721 11099405 · DOI
  129. [143]Harris JS Epps DE Davio SR Kezdy FJ Evidence for transbilayer, tail-to-tail cholesterol dimers in dipalmitoylglycerophosphocholine liposomes Biochemistry 1995 34 3851 3857 10.1021/bi00011a043 7893682 · DOI
  130. [144]Mukherjee S Chattopadhyay A Membrane organization at low cholesterol concentrations: a study using 7-nitrobenz-2-oxa-1,3-diazol-4-yl-labeled cholesterol Biochemistry 1996 35 1311 1322 10.1021/bi951953q 8573588 · DOI
  131. [145]Tulenko TN Chen M Mason PE Mason RP Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis J. Lipid Res. 1998 39 947 956 10.1016/S0022-2275(20)33861-X 9610760 · DOI · Paper page
  132. [147]Xu X London E The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation Biochemistry 2000 39 843 849 10.1021/bi992543v 10653627 · DOI
  133. [148]Pucadyil TJ Chattopadhyay A Role of cholesterol in the function and organization of G-protein coupled receptors Prog. Lipid Res. 2006 45 295 333 10.1016/j.plipres.2006.02.002 16616960 · DOI
  134. [149]Hong C Tontonoz P Liver X receptors in lipid metabolism: opportunities for drug discovery Nat. Rev. Drug Discov. 2014 13 433 444 10.1038/nrd4280 24833295 · DOI · Paper page
  135. [150]Radhakrishnan A Ikeda Y Kwon HJ Brown MS Goldstein JL Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to INSIG Proc. Natl Acad. Sci. USA 2007 104 6511 6518 10.1073/pnas.0700899104 17428920 PMC1851665 · DOI
  136. [151]Mitton JR Scholan NA Boyd GS The oxidation of cholesterol in rat liver sub-cellular particles. The cholesterol-7-alpha-hydroxylase enzyme system Eur. J. Biochem. 1971 20 569 579 10.1111/j.1432-1033.1971.tb01429.x 4397276 · DOI
  137. [152]Cali JJ Russell DW Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis J. Biol. Chem. 1991 266 7774 7778 10.1016/S0021-9258(20)89517-9 1708392 · DOI
  138. [153]Lund EG Kerr TA Sakai J Li WP Russell DW cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism J. Biol. Chem. 1998 273 34316 34327 10.1074/jbc.273.51.34316 9852097 · DOI · Paper page
  139. [154]Lappano R The cholesterol metabolite 25-hydroxycholesterol activates estrogen receptor α-mediated signaling in cancer cells and in cardiomyocytes PLoS One 2011 6 e16631 10.1371/journal.pone.0016631 21304949 PMC3031608 · DOI
  140. [155]Miller WL Strauss JF III Molecular pathology and mechanism of action of the steroidogenic acute regulatory protein, StAR J. Steroid Biochem. Mol. Biol. 1999 69 131 141 10.1016/S0960-0760(98)00153-8 10418987 · DOI · Paper page
  141. [156]Temel RE Brown JM A new model of reverse cholesterol transport: enTICEing strategies to stimulate intestinal cholesterol excretion Trends Pharm. Sci. 2015 36 440 451 10.1016/j.tips.2015.04.002 25930707 PMC4485953 · DOI
  142. [157]Yu XH ABCG5/ABCG8 in cholesterol excretion and atherosclerosis Clin. Chim. Acta 2014 428 82 88 10.1016/j.cca.2013.11.010 24252657 · DOI
  143. [158]Li G Gu HM Zhang DW ATP-binding cassette transporters and cholesterol translocation IUBMB Life 2013 65 505 512 10.1002/iub.1165 23983199 · DOI
  144. [159]Vrins C The sterol transporting heterodimer ABCG5/ABCG8 requires bile salts to mediate cholesterol efflux FEBS Lett. 2007 581 4616 4620 10.1016/j.febslet.2007.08.052 17825296 · DOI
  145. [160]Johnson BJ Lee JY Pickert A Urbatsch IL Bile acids stimulate ATP hydrolysis in the purified cholesterol transporter ABCG5/G8 Biochemistry 2010 49 3403 3411 10.1021/bi902064g 20210363 · DOI
  146. [161]Norlin M Wikvall K Enzymes in the conversion of cholesterol into bile acids Curr. Mol. Med. 2007 7 199 218 10.2174/156652407780059168 17346171 · DOI
  147. [162]de Aguiar Vallim TQ Tarling EJ Edwards PA Pleiotropic roles of bile acids in metabolism Cell Metab. 2013 17 657 669 10.1016/j.cmet.2013.03.013 23602448 PMC3654004 · DOI · Paper page
  148. [163]Ridlon JM Alves JM Hylemon PB Bajaj JS Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship Gut Microbes 2013 4 382 387 10.4161/gmic.25723 23851335 PMC3839982 · DOI · Paper page
  149. [164]Lee JY Crystal structure of the human sterol transporter ABCG5/ABCG8 Nature 2016 533 561 564 10.1038/nature17666 27144356 PMC4964963 · DOI
  150. [165]Back SS Cooperative transcriptional activation of atp-binding cassette sterol transporters ABCG5 and ABCG8 genes by nuclear receptors including Liver-X-Receptor BMB Rep. 2013 46 322 327 10.5483/BMBRep.2013.46.6.246 23790976 PMC4133900 · DOI
  151. [166]van der Veen JN Activation of the liver X receptor stimulates trans-intestinal excretion of plasma cholesterol J. Biol. Chem. 2009 284 19211 19219 10.1074/jbc.M109.014860 19416968 PMC2740545 · DOI
  152. [167]van der Velde AE Brufau G Groen AK Transintestinal cholesterol efflux Curr. Opin. Lipido 2010 21 167 171 10.1097/MOL.0b013e3283395e45 20410820 · DOI
  153. [168]de Boer JF Transintestinal and biliary cholesterol secretion both contribute to macrophage reverse cholesterol transport in rats-brief report Arterioscler Thromb. Vasc. Biol. 2017 37 643 646 10.1161/ATVBAHA.116.308558 28232326 · DOI
  154. [169]Jakulj L Transintestinal cholesterol transport is active in mice and humans and controls ezetimibe-induced fecal neutral sterol excretion Cell Metab. 2016 24 783 794 10.1016/j.cmet.2016.10.001 27818259 · DOI
  155. [170]Temel RE Biliary sterol secretion is not required for macrophage reverse cholesterol transport Cell Metab. 2010 12 96 102 10.1016/j.cmet.2010.05.011 20620999 PMC2913877 · DOI
  156. [171]Stoger JL Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR−/− mice by altering intestinal cholesterol fluxes Thromb. Haemost. 2016 116 565 577 10.1160/TH16-01-0043 27358035 · DOI
  157. [172]Stender S Frikke-Schmidt R Nordestgaard BG Tybjaerg-Hansen A The ABCG5/8 cholesterol transporter and myocardial infarction versus gallstone disease J. Am. Coll. Cardiol. 2014 63 2121 2128 10.1016/j.jacc.2013.12.055 24657701 · DOI
  158. [173]Vrins CLJ Trans-intestinal cholesterol efflux is not mediated through high density lipoprotein J. Lipid Res. 2012 53 2017 2023 10.1194/jlr.M022194 22802462 PMC3435535 · DOI
  159. [174]Le May C Transintestinal cholesterol excretion is an active metabolic process modulated by PCSK9 and statin involving ABCB1 Arterioscler. Thromb. Vasc. Biol. 2013 33 1484 1493 10.1161/ATVBAHA.112.300263 23559630 · DOI
  160. [175]Stange EF Dietschy JM Cholesterol synthesis and low density lipoprotein uptake are regulated independently in rat small intestinal epithelium Proc. Natl Acad. Sci. USA 1983 80 5739 5743 10.1073/pnas.80.18.5739 6310589 PMC384334 · DOI
  161. [176]Tonini, C. et al. Inhibition of bromodomain and extraterminal domain (BET) proteins by JQ1 unravels a novel epigenetic modulation to control lipid homeostasis. Int. J. Mol. Sci. 21 (2020). PMC7072965 32075110
  162. [177]Malhotra P Epigenetic modulation of intestinal cholesterol transporter Niemann-Pick C1-Like 1 (NPC1L1) gene expression by DNA methylation J. Biol. Chem. 2014 289 23132 23140 10.1074/jbc.M113.546283 24904062 PMC4132811 · DOI
  163. [178]Li XJ Deficiency of histone methyltransferase SET domain-containing 2 in liver leads to abnormal lipid metabolism and HCC Hepatology 2021 73 1797 1815 10.1002/hep.31594 33058300 · DOI
  164. [179]Fan Z Brahma related gene 1 (BRG1) regulates cellular cholesterol synthesis by acting as a Co-factor for SREBP2 Front. Cell Dev. Biol. 2020 8 259 10.3389/fcell.2020.00259 32500071 PMC7243037 · DOI
  165. [180]Kim H Choi SY Lim J Lindroth AM Park YJ EHMT2 inhibition induces cell death in human non-small cell lung cancer by altering the cholesterol biosynthesis pathway Int. J. Mol. Sci. 2020 21 1002 10.3390/ijms21031002 PMC7037906 32028644 · DOI
  166. [181]Meaney S Epigenetic regulation of cholesterol homeostasis Front. Genet. 2014 5 311 10.3389/fgene.2014.00311 25309573 PMC4174035 · DOI
  167. [182]Smith Z Ryerson D Kemper JK Epigenomic regulation of bile acid metabolism: emerging role of transcriptional cofactors Mol. Cell Endocrinol. 2013 368 59 70 10.1016/j.mce.2012.04.008 22579755 PMC3473118 · DOI
  168. [183]Chanda D Xie YB Choi HS Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation Nucleic Acids Res 2010 38 4607 4619 10.1093/nar/gkq227 20375098 PMC2919721 · DOI
  169. [184]Shafaati M O’Driscoll R Bjorkhem I Meaney S Transcriptional regulation of cholesterol 24-hydroxylase by histone deacetylase inhibitors Biochem. Biophys. Res. Commun. 2009 378 689 694 10.1016/j.bbrc.2008.11.103 19059217 · DOI
  170. [185]Blanc M The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response Immunity 2013 38 106 118 10.1016/j.immuni.2012.11.004 23273843 PMC3556782 · DOI
  171. [186]Gold ES ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol-induced lipid body formation J. Exp. Med. 2012 209 807 817 10.1084/jem.20111202 22473958 PMC3328364 · DOI
  172. [187]Libby P Atherosclerosis Nat. Rev. Dis. Prim. 2019 5 56 10.1038/s41572-019-0106-z 31420554 · DOI · Paper page
  173. [188]Yu XH Zhang DW Zheng XL Tang CK Cholesterol transport system: an integrated cholesterol transport model involved in atherosclerosis Prog. Lipid Res. 2019 73 65 91 10.1016/j.plipres.2018.12.002 30528667 · DOI
  174. [189]Tabas I Williams KJ Boren J Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therape.utic implications Circulation 2007 116 1832 1844 10.1161/CIRCULATIONAHA.106.676890 17938300 · DOI · Paper page
  175. [190]Huang L SR-BI drives endothelial cell LDL transcytosis via DOCK4 to promote atherosclerosis Nature 2019 569 565 569 10.1038/s41586-019-1140-4 31019307 PMC6631346 · DOI
  176. [191]Tabas I Macrophage death and defective inflammation resolution in atherosclerosis Nat. Rev. Immunol. 2010 10 36 46 10.1038/nri2675 19960040 PMC2854623 · DOI · Paper page
  177. [192]Xu S Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies Pharm. Rev. 2021 73 924 967 10.1124/pharmrev.120.000096 34088867 · DOI
  178. [193]Bobryshev YV Monocyte recruitment and foam cell formation in atherosclerosis Micron 2006 37 208 222 10.1016/j.micron.2005.10.007 16360317 · DOI
  179. [194]Li AC Glass CK The macrophage foam cell as a target for therapeutic intervention Nat. Med. 2002 8 1235 1242 10.1038/nm1102-1235 12411950 · DOI · Paper page
  180. [195]Dickhout JG Basseri S Austin RC Macrophage function and its impact on atherosclerotic lesion composition, progression, and stability: the good, the bad, and the ugly Arterioscler. Thromb. Vasc. Biol. 2008 28 1413 1415 10.1161/ATVBAHA.108.169144 18650503 · DOI
  181. [196]Hutchins PM Heinecke JW Cholesterol efflux capacity, macrophage reverse cholesterol transport and cardioprotective HDL Curr. Opin. Lipido 2015 26 388 393 10.1097/MOL.0000000000000209 PMC4617325 26270810 · DOI
  182. [197]Lao KH Zeng L Xu Q Endothelial and smooth muscle cell transformation in atherosclerosis Curr. Opin. Lipido 2015 26 449 456 10.1097/MOL.0000000000000219 26218417 · DOI
  183. [198]Lusis AJ Atherosclerosis Nature 2000 407 233 241 10.1038/35025203 11001066 PMC2826222 · DOI
  184. [199]Ho-Tin-Noe B Cholesterol crystallization in human atherosclerosis is triggered in smooth muscle cells during the transition from fatty streak to fibroatheroma J. Pathol. 2017 241 671 682 10.1002/path.4873 28039859 · DOI
  185. [200]Abela GS Effect of statins on cholesterol crystallization and atherosclerotic plaque stabilization Am. J. Cardiol. 2011 107 1710 1717 10.1016/j.amjcard.2011.02.336 21507364 · DOI
  186. [201]Vani A Underberg JA Lowering LDL-cholesterol and CV benefits: Is there a limit to how low ldl-c needs to be for optimal health benefits? Clin. Pharm. Ther. 2018 104 290 296 10.1002/cpt.1133 29882959 · DOI
  187. [202]Packard C Chapman MJ Sibartie M Laufs U Masana L Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges Heart 2021 107 1369 1375 10.1136/heartjnl-2020-318760 33795379 PMC8374039 · DOI
  188. [203]Yu D Liao JK Emerging views of statin pleiotropy and cholesterol lowering Cardiovasc. Res. 2022 118 413 423 10.1093/cvr/cvab032 33533892 PMC8803071 · DOI
  189. [206]Ray KK Reductions in atherogenic lipids and major cardiovascular events: a pooled analysis of 10 ODYSSEY trials comparing alirocumab with control Circulation 2016 134 1931 1943 10.1161/CIRCULATIONAHA.116.024604 27777279 PMC5147039 · DOI · Paper page
  190. [207]Cholesterol Treatment Trialists, C. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Lancet 2010 376 1670 1681 10.1016/S0140-6736(10)61350-5 21067804 PMC2988224 · DOI · Paper page
  191. [208]Endo A Kuroda M Tsujita Y ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by penicillium citrinium J. Antibiot. 1976 29 1346 1348 10.7164/antibiotics.29.1346 1010803 · DOI
  192. [209]Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4s) Lancet 1994 344 1383 1389 7968073
  193. [210]Endo A Drugs inhibiting HMG-CoA reductase Pharm. Ther. 1985 31 257 267 10.1016/0163-7258(85)90025-7 3843353 · DOI
  194. [211]Sirtori CR The pharmacology of statins Pharm. Res. 2014 88 3 11 10.1016/j.phrs.2014.03.002 24657242 · DOI
  195. [212]Welder G High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol J. Lipid Res. 2010 51 2714 2721 10.1194/jlr.M008144 20525997 PMC2918453 · DOI
  196. [213]Careskey HE Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9 J. Lipid Res. 2008 49 394 398 10.1194/jlr.M700437-JLR200 18033751 · DOI
  197. [214]Boekholdt SM Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials J. Am. Coll. Cardiol. 2014 64 485 494 10.1016/j.jacc.2014.02.615 25082583 PMC4443441 · DOI · Paper page
  198. [215]Cholesterol Treatment Trialists C Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials Lancet 2019 393 407 415 10.1016/S0140-6736(18)31942-1 30712900 PMC6429627 · DOI · Paper page
  199. [217]Cholesterol Treatment Trialists C The effects of lowering ldl cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials Lancet 2012 380 581 590 10.1016/S0140-6736(12)60367-5 22607822 PMC3437972 · DOI · Paper page
  200. [218]Davignon J Beneficial cardiovascular pleiotropic effects of statins Circulation 2004 109 III39 III43 15198965

200 of 526 shown

Cited by

Sorted by citations

Authors
Duan, Y., Gong, K., Xu, S., Zhang, F., Meng, X., & Han, J.
Affiliations
  • University of Science and Technology of China (CN)
  • Hefei University of Technology (CN)
Corresponding author
Han, Jihong
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2022-08-02
Volume
7
Issue
1
Pages
265-265
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-022-01125-5
PMC
PMC9344793
OpenAlex
W4289521847
Cited by
538
References
58
Citations by year
2026: 148 · 2025: 193 · 2024: 114 · 2023: 73 · 2022: 9 · 2014: 1
FWCI
23.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82173807, 8 197331 6)
  • Nankai University (63211045)
  • Tianjin Science and Technology Committee (20JCZDJC00710)
  • Fundamental Research Funds for the Central Universities (63211045)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
cholesterol homeostasis, cholesterol biosynthesis, cholesterol absorption, cholesterol efflux, LDL cholesterol, atherosclerosis, cardiovascular disease, statins, HMG-CoA reductase inhibition, foam cells, non-alcoholic fatty liver disease, obesity, diabetes mellitus, cancer, neurodegenerative diseases, osteoporosis, viral infection
MeSH terms
Cardiovascular Diseases, Cholesterol, Foam Cells, Homeostasis, Humans, Atherosclerosis

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