{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:37:03Z","timestamp":1773466623435,"version":"3.50.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T00:00:00Z","timestamp":1538524800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T00:00:00Z","timestamp":1538524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Shotgun lipidomic analysis of 203 lipids in 13 lipid classes performed on blood plasma of donors who had just suffered an acute coronary syndrome (ACS,<jats:italic>n<\/jats:italic>\u2009=\u200974), or an ischemic stroke (IS,<jats:italic>n<\/jats:italic>\u2009=\u200921), or who suffer from stable angina pectoris (SAP,<jats:italic>n<\/jats:italic>\u2009=\u200978), and an age-matched control cohort (<jats:italic>n<\/jats:italic>\u2009=\u200952), showed some of the highest inter-lipid class correlations between cholesteryl esters (CE) and phosphatidylcholines (PC) sharing a common fatty acid. The concentration of lysophospatidylcholine (LPC) and ratios of concentrations of CE to free cholesterol (Chol) were also lower in the CVD cohorts than in the control cohort, indicating a deficient conversion of Chol to CE in the blood plasma in the CVD subjects. A non-equilibrium reaction quotient,<jats:italic>Q<\/jats:italic>\u2032, describing the global homeostasis of cholesterol as manifested in the blood plasma was shown to have a value in the CVD cohorts (<jats:italic>Q<\/jats:italic>\u2032<jats:sub>ACS<\/jats:sub>\u2009=\u20090.217\u2009\u00b1\u20090.084;<jats:italic>Q<\/jats:italic>\u2032<jats:sub>IS<\/jats:sub>\u2009=\u20090.201\u2009\u00b1\u20090.084;<jats:italic>Q<\/jats:italic>\u2032<jats:sub>SAP<\/jats:sub>\u2009=\u20090.220\u2009\u00b1\u20090.071) that was about one third less than in the control cohort (<jats:italic>Q<\/jats:italic>\u2032<jats:sub>Control<\/jats:sub>\u2009=\u20090.320\u2009\u00b1\u20090.095,<jats:italic>p<\/jats:italic>\u2009&lt;\u20091\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>), suggesting its potential use as a rapid predictive\/diagnostic measure of CVD-related irregularities in cholesterol homeostasis.<\/jats:p>","DOI":"10.1038\/s41598-018-33116-4","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T13:46:55Z","timestamp":1538056015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients"],"prefix":"10.1038","volume":"8","author":[{"given":"Mathias J.","family":"Gerl","sequence":"first","affiliation":[]},{"given":"Winchil L. C.","family":"Vaz","sequence":"additional","affiliation":[]},{"given":"Neuza","family":"Domingues","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Klose","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7833-2214","authenticated-orcid":false,"given":"Michal A.","family":"Surma","sequence":"additional","affiliation":[]},{"given":"J\u00falio L.","family":"Sampaio","sequence":"additional","affiliation":[]},{"given":"Manuel S.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Gustavo","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Ara\u00fajo-Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Claudia","family":"Borbinha","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Pedro","family":"Marto","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Viana-Baptista","sequence":"additional","affiliation":[]},{"given":"Kai","family":"Simons","sequence":"additional","affiliation":[]},{"given":"Otilia V.","family":"Vieira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,10,3]]},"reference":[{"key":"33116_CR1","doi-asserted-by":"publisher","first-page":"E1183","DOI":"10.1152\/ajpendo.90899.2008","volume":"296","author":"J Iqbal","year":"2009","unstructured":"Iqbal, J. & Hussain, M. M. Intestinal lipid absorption. American journal of physiology. Endocrinology and metabolism 296, E1183\u20131194, https:\/\/doi.org\/10.1152\/ajpendo.90899.2008 (2009).","journal-title":"American journal of physiology. Endocrinology and metabolism"},{"key":"33116_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1097\/00041433-200104000-00008","volume":"12","author":"GS Shelness","year":"2001","unstructured":"Shelness, G. S. & Sellers, J. A. Very-low-density lipoprotein assembly and secretion. Current opinion in lipidology 12, 151\u2013157 (2001).","journal-title":"Current opinion in lipidology"},{"key":"33116_CR3","doi-asserted-by":"publisher","first-page":"17377","DOI":"10.1074\/jbc.R100068200","volume":"277","author":"EA Fisher","year":"2002","unstructured":"Fisher, E. A. & Ginsberg, H. N. Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. The Journal of biological chemistry 277, 17377\u201317380, https:\/\/doi.org\/10.1074\/jbc.R100068200 (2002).","journal-title":"The Journal of biological chemistry"},{"key":"33116_CR4","doi-asserted-by":"publisher","first-page":"14811","DOI":"10.1021\/bi0485629","volume":"43","author":"Y Nakamura","year":"2004","unstructured":"Nakamura, Y. et al. Molecular mechanism of reverse cholesterol transport: reaction of pre-beta-migrating high-density lipoprotein with plasma lecithin\/cholesterol acyltransferase. Biochemistry 43, 14811\u201314820, https:\/\/doi.org\/10.1021\/bi0485629 (2004).","journal-title":"Biochemistry"},{"key":"33116_CR5","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.jacc.2007.09.060","volume":"51","author":"WA van der Steeg","year":"2008","unstructured":"van der Steeg, W. A. et al. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. Journal of the American College of Cardiology 51, 634\u2013642, https:\/\/doi.org\/10.1016\/j.jacc.2007.09.060 (2008).","journal-title":"Journal of the American College of Cardiology"},{"key":"33116_CR6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1097\/MOL.0b013e328338472d","volume":"21","author":"GH Rothblat","year":"2010","unstructured":"Rothblat, G. H. & Phillips, M. C. High-density lipoprotein heterogeneity and function in reverse cholesterol transport. Current opinion in lipidology 21, 229\u2013238 (2010).","journal-title":"Current opinion in lipidology"},{"key":"33116_CR7","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1038\/nm.2930","volume":"18","author":"JW Heinecke","year":"2012","unstructured":"Heinecke, J. W. The not-so-simple HDL story: A new era for quantifying HDL and cardiovascular risk? Nature medicine 18, 1346\u20131347, https:\/\/doi.org\/10.1038\/nm.2930 (2012).","journal-title":"Nature medicine"},{"key":"33116_CR8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1161\/CIRCRESAHA.114.300632","volume":"114","author":"KA Rye","year":"2014","unstructured":"Rye, K. A. & Barter, P. J. Regulation of high-density lipoprotein metabolism. Circulation research 114, 143\u2013156, https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.300632 (2014).","journal-title":"Circulation research"},{"key":"33116_CR9","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/S0140-6736(14)61217-4","volume":"384","author":"DJ Rader","year":"2014","unstructured":"Rader, D. J. & Hovingh, G. K. HDL and cardiovascular disease. Lancet 384, 618\u2013625, https:\/\/doi.org\/10.1016\/S0140-6736(14)61217-4 (2014).","journal-title":"Lancet"},{"key":"33116_CR10","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1001\/jama.2016.13985","volume":"316","author":"MG Silverman","year":"2016","unstructured":"Silverman, M. G. et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. Jama 316, 1289\u20131297, https:\/\/doi.org\/10.1001\/jama.2016.13985 (2016).","journal-title":"Jama"},{"key":"33116_CR11","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1093\/cvr\/cvu147","volume":"103","author":"A Kontush","year":"2014","unstructured":"Kontush, A. HDL-mediated mechanisms of protection in cardiovascular disease. Cardiovascular research 103, 341\u2013349, https:\/\/doi.org\/10.1093\/cvr\/cvu147 (2014).","journal-title":"Cardiovascular research"},{"key":"33116_CR12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1161\/CIRCRESAHA.114.300935","volume":"114","author":"TF Luscher","year":"2014","unstructured":"Luscher, T. F., Landmesser, U., von Eckardstein, A. & Fogelman, A. M. High-density lipoprotein: vascular protective effects, dysfunction, and potential as therapeutic target. Circulation research 114, 171\u2013182, https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.300935 (2014).","journal-title":"Circulation research"},{"key":"33116_CR13","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1194\/jlr.R039297","volume":"55","author":"KA Rye","year":"2014","unstructured":"Rye, K. A. & Barter, P. J. Cardioprotective functions of HDLs. Journal of lipid research 55, 168\u2013179, https:\/\/doi.org\/10.1194\/jlr.R039297 (2014).","journal-title":"Journal of lipid research"},{"key":"33116_CR14","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1002\/ejlt.201500145","volume":"117","author":"MA Surma","year":"2015","unstructured":"Surma, M. A. et al. An automated shotgun lipidomics platform for high throughput, comprehensive, and quantitative analysis of blood plasma intact lipids. European journal of lipid science and technology: EJLST 117, 1540\u20131549, https:\/\/doi.org\/10.1002\/ejlt.201500145 (2015).","journal-title":"European journal of lipid science and technology: EJLST"},{"key":"33116_CR15","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1016\/j.jacc.2007.11.075","volume":"51","author":"B Pitt","year":"2008","unstructured":"Pitt, B., Loscalzo, J., Ycas, J. & Raichlen, J. S. Lipid levels after acute coronary syndromes. Journal of the American College of Cardiology 51, 1440\u20131445, https:\/\/doi.org\/10.1016\/j.jacc.2007.11.075 (2008).","journal-title":"Journal of the American College of Cardiology"},{"key":"33116_CR16","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1373\/clinchem.2010.145631","volume":"56","author":"JH Barth","year":"2010","unstructured":"Barth, J. H. et al. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clinical chemistry 56, 1592\u20131598, https:\/\/doi.org\/10.1373\/clinchem.2010.145631 (2010).","journal-title":"Clinical chemistry"},{"key":"33116_CR17","doi-asserted-by":"publisher","first-page":"e71846","DOI":"10.1371\/journal.pone.0071846","volume":"8","author":"C Fernandez","year":"2013","unstructured":"Fernandez, C. et al. Plasma lipid composition and risk of developing cardiovascular disease. PloS one 8, e71846, https:\/\/doi.org\/10.1371\/journal.pone.0071846 (2013).","journal-title":"PloS one"},{"key":"33116_CR18","doi-asserted-by":"crossref","unstructured":"Vance, D. E. Phopholipid biosynthesis in eukaryotes. 5th edn, 213\u2013244 (Elsevier Science, 2008).","DOI":"10.1016\/B978-044453219-0.50010-6"},{"key":"33116_CR19","doi-asserted-by":"publisher","first-page":"4064","DOI":"10.1529\/biophysj.104.054007","volume":"88","author":"JL Sampaio","year":"2005","unstructured":"Sampaio, J. L., Moreno, M. J. & Vaz, W. L. Kinetics and thermodynamics of association of a fluorescent lysophospholipid derivative with lipid bilayers in liquid-ordered and liquid-disordered phases. Biophysical journal 88, 4064\u20134071, https:\/\/doi.org\/10.1529\/biophysj.104.054007 (2005).","journal-title":"Biophysical journal"},{"key":"33116_CR20","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1529\/biophysj.104.040576","volume":"87","author":"MS Abreu","year":"2004","unstructured":"Abreu, M. S., Moreno, M. J. & Vaz, W. L. Kinetics and thermodynamics of association of a phospholipid derivative with lipid bilayers in liquid-disordered and liquid-ordered phases. Biophysical journal 87, 353\u2013365, https:\/\/doi.org\/10.1529\/biophysj.104.040576 (2004).","journal-title":"Biophysical journal"},{"key":"33116_CR21","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1529\/biophysj.104.047050","volume":"88","author":"LM Estronca","year":"2005","unstructured":"Estronca, L. M., Moreno, M. J., Laranjinha, J. A., Almeida, L. M. & Vaz, W. L. Kinetics and thermodynamics of lipid amphiphile exchange between lipoproteins and albumin in serum. Biophysical journal 88, 557\u2013565, https:\/\/doi.org\/10.1529\/biophysj.104.047050 (2005).","journal-title":"Biophysical journal"},{"key":"33116_CR22","doi-asserted-by":"publisher","first-page":"4244","DOI":"10.1529\/biophysj.107.112847","volume":"93","author":"LM Estronca","year":"2007","unstructured":"Estronca, L. M., Moreno, M. J. & Vaz, W. L. Kinetics and thermodynamics of the association of dehydroergosterol with lipid bilayer membranes. Biophysical journal 93, 4244\u20134253, https:\/\/doi.org\/10.1529\/biophysj.107.112847 (2007).","journal-title":"Biophysical journal"},{"key":"33116_CR23","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1194\/jlr.M043067","volume":"55","author":"LM Estronca","year":"2014","unstructured":"Estronca, L. M., Filipe, H. A., Salvador, A., Moreno, M. J. & Vaz, W. L. Homeostasis of free cholesterol in the blood: a preliminary evaluation and modeling of its passive transport. Journal of lipid research 55, 1033\u20131043, https:\/\/doi.org\/10.1194\/jlr.M043067 (2014).","journal-title":"Journal of lipid research"},{"key":"33116_CR24","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.1194\/jlr.M009449","volume":"51","author":"O Quehenberger","year":"2010","unstructured":"Quehenberger, O. et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. Journal of lipid research 51, 3299\u20133305, https:\/\/doi.org\/10.1194\/jlr.M009449 (2010).","journal-title":"Journal of lipid research"},{"key":"33116_CR25","doi-asserted-by":"publisher","first-page":"13259","DOI":"10.1021\/bi00249a012","volume":"33","author":"PV Subbaiah","year":"1994","unstructured":"Subbaiah, P. V., Liu, M. & Paltauf, F. Role of sn-2 acyl group of phosphatidylcholine in determining the positional specificity of lecithin-cholesterol acyltransferase. Biochemistry 33, 13259\u201313266 (1994).","journal-title":"Biochemistry"},{"key":"33116_CR26","doi-asserted-by":"publisher","first-page":"13626","DOI":"10.1021\/bi980351e","volume":"37","author":"M Liu","year":"1998","unstructured":"Liu, M., Subramanian, V. S. & Subbaiah, P. V. Modulation of the positional specificity of lecithin-cholesterol acyltransferase by the acyl group composition of its phosphatidylcholine substrate: role of the sn-1-acyl group. Biochemistry 37, 13626\u201313633, https:\/\/doi.org\/10.1021\/bi980351e (1998).","journal-title":"Biochemistry"},{"key":"33116_CR27","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1194\/jlr.D300020-JLR200","volume":"44","author":"K Ekroos","year":"2003","unstructured":"Ekroos, K. et al. Charting molecular composition of phosphatidylcholines by fatty acid scanning and ion trap MS3 fragmentation. Journal of lipid research 44, 2181\u20132192, https:\/\/doi.org\/10.1194\/jlr.D300020-JLR200 (2003).","journal-title":"Journal of lipid research"},{"key":"33116_CR28","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/978-1-4419-1059-2_3","volume-title":"High Density Lipoproteins, Dyslipidemia, and Coronary Heart Disease","author":"Bela F. Asztalos","year":"2010","unstructured":"Asztalos, B. F. High density lipoprotein particles., 25 (Springer, New York, 2010)."},{"key":"33116_CR29","doi-asserted-by":"publisher","first-page":"119","DOI":"10.5551\/jat.32854","volume":"23","author":"A Ossoli","year":"2016","unstructured":"Ossoli, A., Simonelli, S., Vitali, C., Franceschini, G. & Calabresi, L. Role of LCAT in Atherosclerosis. Journal of atherosclerosis and thrombosis 23, 119\u2013127, https:\/\/doi.org\/10.5551\/jat.32854 (2016).","journal-title":"Journal of atherosclerosis and thrombosis"},{"key":"33116_CR30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.33549\/physiolres.933621","volume":"66","author":"M Dobiasova","year":"2017","unstructured":"Dobiasova, M. Atherogenic impact of lecithin-cholesterol acyltransferase and its relation to cholesterol esterification rate in HDL (FER(HDL)) and AIP [log(TG\/HDL-C)] biomarkers: the butterfly effect? Physiological research 66, 193\u2013203 (2017).","journal-title":"Physiological research"},{"key":"33116_CR31","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1194\/P900038-JLR200","volume":"51","author":"AG Holleboom","year":"2010","unstructured":"Holleboom, A. G. et al. Plasma levels of lecithin:cholesterol acyltransferase and risk of future coronary artery disease in apparently healthy men and women: a prospective case-control analysis nested in the EPIC-Norfolk population study. Journal of lipid research 51, 416\u2013421, https:\/\/doi.org\/10.1194\/P900038-JLR200 (2010).","journal-title":"Journal of lipid research"},{"key":"33116_CR32","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1056\/NEJMoa1001689","volume":"364","author":"AV Khera","year":"2011","unstructured":"Khera, A. V. et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. The New England journal of medicine 364, 127\u2013135, https:\/\/doi.org\/10.1056\/NEJMoa1001689 (2011).","journal-title":"The New England journal of medicine"},{"key":"33116_CR33","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S2213-8587(15)00126-6","volume":"3","author":"D Saleheen","year":"2015","unstructured":"Saleheen, D. et al. Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study. The lancet. Diabetes & endocrinology 3, 507\u2013513, https:\/\/doi.org\/10.1016\/S2213-8587(15)00126-6 (2015).","journal-title":"The lancet. Diabetes & endocrinology"},{"key":"33116_CR34","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0005-2736(98)00260-0","volume":"1417","author":"J Huang","year":"1999","unstructured":"Huang, J., Buboltz, J. T. & Feigenson, G. W. Maximum solubility of cholesterol in phosphatidylcholine and phosphatidylethanolamine bilayers. Biochimica et biophysica acta 1417, 89\u2013100 (1999).","journal-title":"Biochimica et biophysica acta"},{"key":"33116_CR35","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/S0014-5793(99)00278-1","volume":"447","author":"A Davit-Spraul","year":"1999","unstructured":"Davit-Spraul, A. et al. Inhibition of lecithin cholesterol acyltransferase by phosphatidylcholine hydroperoxides. FEBS letters 447, 106\u2013110 (1999).","journal-title":"FEBS letters"},{"key":"33116_CR36","doi-asserted-by":"publisher","first-page":"38517","DOI":"10.1074\/jbc.M205924200","volume":"277","author":"EA Podrez","year":"2002","unstructured":"Podrez, E. A. et al. A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. The Journal of biological chemistry 277, 38517\u201338523, https:\/\/doi.org\/10.1074\/jbc.M205924200 (2002).","journal-title":"The Journal of biological chemistry"},{"key":"33116_CR37","doi-asserted-by":"publisher","first-page":"e34822","DOI":"10.1371\/journal.pone.0034822","volume":"7","author":"LM Estronca","year":"2012","unstructured":"Estronca, L. M. et al. Molecular etiology of atherogenesis\u2013in vitro induction of lipidosis in macrophages with a new LDL model. PloS one 7, e34822, https:\/\/doi.org\/10.1371\/journal.pone.0034822 (2012).","journal-title":"PloS one"},{"key":"33116_CR38","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.bbalip.2016.10.009","volume":"1862","author":"N Domingues","year":"2017","unstructured":"Domingues, N. et al. Cholesteryl hemiesters alter lysosome structure and function and induce proinflammatory cytokine production in macrophages. Biochimica et biophysica acta 1862, 210\u2013220, https:\/\/doi.org\/10.1016\/j.bbalip.2016.10.009 (2017).","journal-title":"Biochimica et biophysica acta"},{"key":"33116_CR39","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0022-2275(20)42061-9","volume":"32","author":"MC Cheung","year":"1991","unstructured":"Cheung, M. C., Brown, B. G., Wolf, A. C. & Albers, J. J. Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease. Journal of lipid research 32, 383\u2013394 (1991).","journal-title":"Journal of lipid research"},{"key":"33116_CR40","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1161\/01.ATV.0000146325.93749.a8","volume":"24","author":"BF Asztalos","year":"2004","unstructured":"Asztalos, B. F. et al. High-density lipoprotein subpopulation profile and coronary heart disease prevalence in male participants of the Framingham Offspring Study. Arteriosclerosis, thrombosis, and vascular biology 24, 2181\u20132187, https:\/\/doi.org\/10.1161\/01.ATV.0000146325.93749.a8 (2004).","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"key":"33116_CR41","doi-asserted-by":"publisher","first-page":"e85114","DOI":"10.1371\/journal.pone.0085114","volume":"9","author":"L Tian","year":"2014","unstructured":"Tian, L., Li, C., Liu, Y., Chen, Y. & Fu, M. The value and distribution of high-density lipoprotein subclass in patients with acute coronary syndrome. PloS one 9, e85114, https:\/\/doi.org\/10.1371\/journal.pone.0085114 (2014).","journal-title":"PloS one"},{"key":"33116_CR42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0022-2275(20)37433-2","volume":"38","author":"JA Kuivenhoven","year":"1997","unstructured":"Kuivenhoven, J. A. et al. The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes. Journal of lipid research 38, 191\u2013205 (1997).","journal-title":"Journal of lipid research"},{"key":"33116_CR43","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1161\/01.ATV.0000175751.30616.13","volume":"25","author":"L Calabresi","year":"2005","unstructured":"Calabresi, L. et al. The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families. Arteriosclerosis, thrombosis, and vascular biology 25, 1972\u20131978, https:\/\/doi.org\/10.1161\/01.ATV.0000175751.30616.13 (2005).","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"key":"33116_CR44","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-013-0326-8","volume":"15","author":"JC van Capelleveen","year":"2013","unstructured":"van Capelleveen, J. C., Bochem, A. E., Motazacker, M. M., Hovingh, G. K. & Kastelein, J. J. Genetics of HDL-C: a causal link to atherosclerosis? Current atherosclerosis reports 15, 326, https:\/\/doi.org\/10.1007\/s11883-013-0326-8 (2013).","journal-title":"Current atherosclerosis reports"},{"key":"33116_CR45","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1194\/jlr.R024513","volume":"53","author":"S Kunnen","year":"2012","unstructured":"Kunnen, S. & Van Eck, M. Lecithin:cholesterol acyltransferase: old friend or foe in atherosclerosis? Journal of lipid research 53, 1783\u20131799, https:\/\/doi.org\/10.1194\/jlr.R024513 (2012).","journal-title":"Journal of lipid research"},{"key":"33116_CR46","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.bbalip.2011.12.012","volume":"1821","author":"DS Ng","year":"2012","unstructured":"Ng, D. S. The role of lecithin:cholesterol acyltransferase in the modulation of cardiometabolic risks - a clinical update and emerging insights from animal models. Biochimica et biophysica acta 1821, 654\u2013659, https:\/\/doi.org\/10.1016\/j.bbalip.2011.12.012 (2012).","journal-title":"Biochimica et biophysica acta"},{"key":"33116_CR47","doi-asserted-by":"publisher","first-page":"2860","DOI":"10.1093\/bioinformatics\/btv285","volume":"31","author":"L Aimo","year":"2015","unstructured":"Aimo, L. et al. The SwissLipids knowledgebase for lipid biology. Bioinformatics 31, 2860\u20132866, https:\/\/doi.org\/10.1093\/bioinformatics\/btv285 (2015).","journal-title":"Bioinformatics"},{"key":"33116_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-1-r8","volume":"12","author":"R Herzog","year":"2011","unstructured":"Herzog, R. et al. A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language. Genome biology 12, R8, https:\/\/doi.org\/10.1186\/gb-2011-12-1-r8 (2011).","journal-title":"Genome biology"},{"key":"33116_CR49","doi-asserted-by":"publisher","first-page":"e29851","DOI":"10.1371\/journal.pone.0029851","volume":"7","author":"R Herzog","year":"2012","unstructured":"Herzog, R. et al. LipidXplorer: a software for consensual cross-platform lipidomics. PloS one 7, e29851, https:\/\/doi.org\/10.1371\/journal.pone.0029851 (2012).","journal-title":"PloS one"},{"key":"33116_CR50","unstructured":"Team, R. C. R: A Language and Environment for Statistical Computing, https:\/\/www.R-project.org\/ (2017)."},{"key":"33116_CR51","doi-asserted-by":"crossref","unstructured":"Wickham, H. tidyverse: Easily Install and Load \u2018Tidyverse\u2019 Packages, https:\/\/CRAN.R-project.org\/package=tidyverse (2017).","DOI":"10.32614\/CRAN.package.tidyverse"},{"key":"33116_CR52","doi-asserted-by":"crossref","unstructured":"Wickham, H. ggplot2: Elegant Graphics for Data Analysis. (New York Springer - Verlag, New York; 2009).","DOI":"10.1007\/978-0-387-98141-3"},{"key":"33116_CR53","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research 13, 2498\u20132504, https:\/\/doi.org\/10.1101\/gr.1239303 (2003).","journal-title":"Genome research"},{"key":"33116_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v028.i05","volume":"28","author":"M Kuhn","year":"2008","unstructured":"Kuhn, M. Building Predictive Models in R Using the caret Package. J Stat Softw 28, 1\u201326 (2008).","journal-title":"J Stat Softw"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33116-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33116-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33116-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T20:44:24Z","timestamp":1720644264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-33116-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,3]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["33116"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-33116-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,3]]},"assertion":[{"value":"7 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"14764"}}