GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the global burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210.

Google Scholar 

Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72.

PubMed  PubMed Central  Google Scholar 

Yusuf S, Joseph P, Rangarajan S, Islam S, Mente A, Hystad P, et al. Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet. 2020;395(10226):795–808.

PubMed  Google Scholar 

Johannesen CDL, Mortensen MB, Langsted A, Nordestgaard BG. Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk than LDL Cholesterol in statin-treated patients. J Am Coll Cardiol. 2021;77(11):1439–50.

PubMed  Google Scholar 

Tokgözoğlu L, Libby P. The dawn of a new era of targeted lipid-lowering therapies. European Heart Journal [Internet]. 2022 Sep 7 [cited 2024 Jul 16];43(34):3198–208. https://academic.oup.com/eurheartj/article/43/34/3198/6512083

Ginsberg HN, Packard CJ, Chapman MJ, Borén J, Aguilar-Salinas CA, Averna M, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021;42(47):4791–806.

PubMed  PubMed Central  Google Scholar 

Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35.

PubMed  Google Scholar 

Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease. Journal of the American College of Cardiology [Internet]. 2013 Jan [cited 2024 Jul 16];61(4):427–36. https://linkinghub.elsevier.com/retrieve/pii/S0735109712055222

Zhong VW, Van Horn L, Cornelis MC, Wilkins JT, Ning H, Carnethon MR, et al. Associations of Dietary cholesterol or egg consumption with Incident Cardiovascular Disease and Mortality. JAMA. 2019;321(11):1081–95.

PubMed  PubMed Central  Google Scholar 

Taskinen MR, Matikainen N, Björnson E, Söderlund S, Inkeri J, Hakkarainen A, et al. Contribution of intestinal triglyceride-rich lipoproteins to residual atherosclerotic cardiovascular disease risk in individuals with type 2 diabetes on statin therapy. Diabetologia. 2023;66(12):2307–19.

PubMed  PubMed Central  Google Scholar 

Ko CW, Qu J, Black DD, Tso P. Regulation of intestinal lipid metabolism: current concepts and relevance to disease. Nat Rev Gastroenterol Hepatol. 2020;17(3):169–83.

PubMed  Google Scholar 

Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020;21(4):225–45.

PubMed  Google Scholar 

van der Velde AE, Vrins CLJ, van den Oever K, Kunne C, Oude Elferink RPJ, Kuipers F, et al. Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice. Gastroenterology. 2007;133(3):967–75.

PubMed  Google Scholar 

Garçon D, Berger JM, Cariou B, Le May C. Transintestinal cholesterol excretion in health and disease. Curr Atheroscler Rep. 2022;24(3):153–60.

PubMed  Google Scholar 

Duval C, Touche V, Tailleux A, Fruchart JC, Fievet C, Clavey V, et al. Niemann-pick C1 like 1 gene expression is down-regulated by LXR activators in the intestine. Biochem Biophys Res Commun. 2006;340(4):1259–63.

PubMed  Google Scholar 

Lo Sasso G, Murzilli S, Salvatore L, D’Errico I, Petruzzelli M, Conca P, et al. Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. Cell Metab. 2010;12(2):187–93.

PubMed  Google Scholar 

Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem. 2002;277(21):18793–800.

PubMed  Google Scholar 

Venkateswaran A, Laffitte BA, Joseph SB, Mak PA, Wilpitz DC, Edwards PA, et al. Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha. Proc Natl Acad Sci U S A. 2000;97(22):12097–102.

PubMed  PubMed Central  Google Scholar 

Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, et al. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest. 2006;116(4):1052–62.

PubMed  PubMed Central  Google Scholar 

van der Veen JN, van Dijk TH, Vrins CLJ, van Meer H, Havinga R, Bijsterveld K, et al. Activation of the liver X receptor stimulates trans-intestinal excretion of plasma cholesterol. J Biol Chem. 2009;284(29):19211–9.

PubMed  PubMed Central  Google Scholar 

Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, et al. Role of LXRs in control of lipogenesis. Genes Dev. 2000;14(22):2831–8.

PubMed  PubMed Central  Google Scholar 

Grefhorst A, Elzinga BM, Voshol PJ, Plösch T, Kok T, Bloks VW, et al. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem. 2002;277(37):34182–90.

PubMed  Google Scholar 

Yasuda T, Grillot D, Billheimer JT, Briand F, Delerive P, Huet S, et al. Tissue-specific liver X receptor activation promotes macrophage reverse cholesterol transport in vivo. Arterioscler Thromb Vasc Biol. 2010;30(4):781–6.

PubMed  PubMed Central  Google Scholar 

Li N, Wang X, Xu Y, Lin Y, Zhu N, Liu P, et al. Identification of a Novel Liver X receptor agonist that regulates the expression of key cholesterol homeostasis genes with distinct pharmacological characteristics. Mol Pharmacol. 2017;91(4):264–76.

PubMed  Google Scholar 

Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nat Rev Genet. 2009;10(2):109–21.

PubMed  Google Scholar 

Graham SE, Clarke SL, Wu KHH, Kanoni S, Zajac GJM, Ramdas S, et al. The power of genetic diversity in genome-wide association studies of lipids. Nature. 2021;600(7890):675–9.

PubMed  PubMed Central  Google Scholar 

Altmann SW, Davis HR, Zhu LJ, Yao X, Hoos LM, Tetzloff G, et al. Niemann-pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303(5661):1201–4.

PubMed  Google Scholar 

Xie 谢畅 C, Zhou 周章森 ZS, Li 李钠 N, Bian 卞艳 Y, Wang 王永建 YJ, Wang 王丽娟 LJ, et al. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine. J Lipid Res. 2012;53(10):2092–101.

PubMed  PubMed Central  Google Scholar 

Ge L, Qi W, Wang LJ, Miao HH, Qu YX, Li BL, et al. Flotillins play an essential role in Niemann-pick C1-like 1-mediated cholesterol uptake. Proc Natl Acad Sci U S A. 2011;108(2):551–6.

PubMed  Google Scholar 

Li PS, Fu ZY, Zhang YY, Zhang JH, Xu CQ, Ma YT, et al. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nat Med. 2014;20(1):80–6.

PubMed  Google Scholar 

Zhang YY, Fu ZY, Wei J, Qi W, Baituola G, Luo J, et al. A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption. Science. 2018;360(6393):1087–92.

PubMed  Google Scholar 

Buhman KK, Accad M, Novak S, Choi RS, Wong JS, Hamilton RL, et al. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med. 2000;6(12):1341–7.

PubMed  Google Scholar 

Zhang J, Sawyer JK, Marshall SM, Kelley KL, Davis MA, Wilson MD, et al. Cholesterol esters (CE) derived from hepatic sterol O-acyltransferase 2 (SOAT2) are associated with more atherosclerosis than CE from intestinal SOAT2. Circ Res. 2014;115(10):826–33.

PubMed  PubMed Central  Google Scholar 

Ferrari A, Whang E, Xiao X, Kennelly JP, Romartinez-Alonso B, Mack JJ, et al. Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake. Science. 2023;382(6671):eadf0966.

PubMed  PubMed Central  Google Scholar 

Xiao J, Dong LW, Liu S, Meng FH, Xie C, Lu XY, et al. Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling. Nat Commun. 2023;14(1):6469.

PubMed  PubMed Central  Google Scholar 

Thierer JH, Foresti O, Yadav PK, Wilson MH, Moll TOC, Shen MC, et al. Pla2g12b drives expansion of triglyceride-rich lipoproteins. Nat Commun. 2024;15(1):2095.

PubMed  PubMed Central  Google Scholar 

Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, et al. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature. 1993;365(6441):65–9.

PubMed  Google Scholar 

Kohan AB, Wang F, Li X, Bradshaw S, Yang Q, Caldwell JL, et al. Apolipoprotein A-IV regulates chylomicron metabolism-mechanism and function. Am J Physiol Gastrointest Liver Physiol. 2012;302(6):G628–636.

PubMed  Google Scholar 

Siddiqi S, Saleem U, Abumrad NA, Davidson NO, Storch J, Siddiqi SA, et al. A novel multiprotein complex is required to generate the prechylomicron transport vesicle from intestinal ER. J Lipid Res. 2010;51(7):1918–28.

PubMed  PubMed Central  Google Scholar 

Siddiqi SA, Mahan J, Siddiqi S, Gorelick FS, Mansbach CM. Vesicle-associated membrane protein 7 is expressed in intestinal ER. J Cell Sci. 2006;119(Pt 5):943–50.

PubMed  Google Scholar 

Siddiqi S, Mansbach CM. Phosphorylation of Sar1b protein releases liver fatty acid-binding protein from multiprotein complex in intestinal cytosol enabling it to bind to endoplasmic reticulum (ER) and bud the pre-chylomicron transport vesicle. J Biol Chem. 2012;287(13):10178–88.

PubMed  PubMed Central