{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T12:17:32Z","timestamp":1793621852200,"version":"4.5.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"9","license":[{"start":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:00:00Z","timestamp":1471305600000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.pnas.org\/preview_site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["HL093234"],"award-info":[{"award-number":["HL093234"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["HL093234--S1"],"award-info":[{"award-number":["HL093234--S1"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["HL125275"],"award-info":[{"award-number":["HL125275"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DA1209\/1-1"],"award-info":[{"award-number":["DA1209\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-115160"],"award-info":[{"award-number":["MOP-115160"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Major infections, such as influenza and bacterial sepsis, kill millions of individuals yearly, most commonly from complications affecting the vasculature, such as acute respiratory distress syndrome. Poor outcomes from rare infections, such as Ebola virus disease, have also been linked to the vasculature. The basis for prominent vascular involvement in infectious syndromes remains poorly understood. The present work shows that humans exhibit common, yet highly consequential, genetic variation in the ability to sustain expression of a key homeostatic vascular receptor called tunica interna endothelial cell kinase 2. The results suggest that host determinants of the molecular vascular response to infection may have a heretofore underappreciated impact on clinical outcomes. They also suggest new means to identify at-risk individuals and personalize future therapies.<\/jats:p>","DOI":"10.1073\/pnas.1519467113","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T23:10:11Z","timestamp":1455664211000},"page":"2472-2477","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":102,"title":["Gene control of tyrosine kinase\n                    <i>TIE2<\/i>\n                    and vascular manifestations of infections"],"prefix":"10.1073","volume":"113","author":[{"given":"Chandra C.","family":"Ghosh","sequence":"first","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"David","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"},{"name":"Division of Hypertension and Nephrology, Hannover Medical School, 30625 Hannover, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114;"},{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Berghelli","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Milam","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"},{"name":"Sandra Rotman Centre for Global Health, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Hunter","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyue","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114;"},{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freeman","family":"Suber","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lester","family":"Kobzik","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Kain","sequence":"additional","affiliation":[{"name":"Sandra Rotman Centre for Global Health, University Health Network and Department of Medicine, University of Toronto, Toronto, ON, Canada M5S 1A1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar","family":"Santel","sequence":"additional","affiliation":[{"name":"Silence Therapeutics GmbH, 13125 Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiichiro","family":"Yano","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prajna","family":"Guha","sequence":"additional","affiliation":[{"name":"Roger Williams Medical Center, Providence, RI 02908;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Dumont","sequence":"additional","affiliation":[{"name":"Sunnybrook Institute, University of Toronto, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Christiani","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114;"},{"name":"Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir M.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31825fdc31"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01472-08"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58832"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1351"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01653"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66549"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.4.567"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/74725"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5449.2511"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46322"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507082"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000158285.57191.60"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100282200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.24906"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702169200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000151287.08202.8E"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000000524"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120755109"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00459.2010"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.11.3.571"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090389"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002011"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1208623"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08903"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.10.1177"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.29.20376"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-013-0358-9"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421801"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181cc4824"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1494"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6962"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1715"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.856815"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202992"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200811159"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.10.019"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131190"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-013-2899-7"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.150482"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02397-07"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1259595"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302777"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12531"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-1246"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg393"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.214"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0349OC"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-105"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030046"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.233189"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-375816"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.116"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111343"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1519467113","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1519467113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:59:13Z","timestamp":1649811553000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1519467113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,16]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1073\/pnas.1519467113"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1519467113","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,16]]},"assertion":[{"value":"2016-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}