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Here, we describe the human experimental endotoxemia model for the specific study of innate immunity in understanding further the pathogenesis of cardiometabolic disease. In a controlled, experimental setting, administration of an intravenous bolus of purified\n            <jats:italic>Escherichia coli<\/jats:italic>\n            endotoxin activates innate immunity in healthy human volunteers. During endotoxemia, changes emerge in glucose metabolism, lipoprotein composition, and lipoprotein functions that closely resemble those observed chronically in inflammatory cardiovascular disease risk states. In this review, we describe the transient systemic inflammation and specific metabolic consequences that develop during human endotoxemia. Such a model provides a controlled induction of systemic inflammation, eliminates confounding, undermines reverse causation, and possesses unique potential as a starting point for genomic screening and testing of novel therapeutics for treatment of the inflammatory underpinning of cardiometabolic disease.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.114.304455","type":"journal-article","created":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T05:39:52Z","timestamp":1420004392000},"page":"525-534","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases"],"prefix":"10.1161","volume":"35","author":[{"given":"Parth N.","family":"Patel","sequence":"first","affiliation":[{"name":"From the Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (P.N.P., R.Y.S., M.P.R.); and Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (J.F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhia Y.","family":"Shah","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (P.N.P., R.Y.S., M.P.R.); and Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (J.F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane F.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (P.N.P., R.Y.S., M.P.R.); and Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (J.F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muredach P.","family":"Reilly","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (P.N.P., R.Y.S., M.P.R.); and Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, TN (J.F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5418.1313"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008033430506"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.3.813"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxh186"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2011.05.039"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03203.x"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080502"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986708784872393"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpa.2003.12.002"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.002253"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2119\/2007-00135.Ferwerda"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001073"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.1648"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1116"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161208784980563"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.2951058"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28898"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403249101"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1595"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29069"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0802501"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0938"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198908033210503"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.27.020176.001015"},{"key":"e_1_3_4_27_2","first-page":"280","article-title":"Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings.","volume":"104","author":"Michie HR","year":"1988","unstructured":"Michie HR, Spriggs DR, Manogue KR, Sherman ML, Revhaug A, O\u2019Dwyer ST, Arthur K, Dinarello CA, Cerami A, Wolff SM. 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