{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T08:20:27Z","timestamp":1793089227494,"version":"4.5.0"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Most of the circulating sphingosine\u20101\u2010phosphate (S1P) is bound to ApoM (apolipoprotein M) of high\u2010density lipoprotein (HDL) and mediates many beneficial effects of HDL on the vasculature via G protein\u2013coupled S1P receptors. HDL\u2010bound S1P is decreased in atherosclerosis, myocardial infarction, and diabetes mellitus. In addition to being the target, the endothelium is a source of S1P, which is transported outside of the cells by Spinster\u20102, contributing to circulating S1P as well as to local signaling. Mice lacking endothelial S1P receptor 1 are hypertensive, suggesting a vasculoprotective role of S1P signaling. This study investigates the role of endothelial\u2010derived S1P and ApoM\u2010bound S1P in regulating vascular tone and blood pressure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">ApoM knockout (ApoM KO) mice and mice lacking endothelial Spinster\u20102 (ECKO\u2010Spns2) were infused with angiotensin II for 28\u00a0days. Blood pressure, measured by telemetry and tail\u2010cuff, was significantly increased in both ECKO\u2010Spns2 and ApoM KO versus control mice, at baseline and following angiotensin II. Notably, ECKO\u2010Spns2 presented an impaired vasodilation to flow and blood pressure dipping, which is clinically associated with increased risk for cardiovascular events. In hypertension, both groups presented reduced flow\u2010mediated vasodilation and some degree of impairment in endothelial NO production, which was more evident in ECKO\u2010Spns2. Increased hypertension in ECKO\u2010Spns2 and ApoM KO mice correlated with worsened cardiac hypertrophy versus controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our study identifies an important role for Spinster\u20102 and ApoM\u2010HDL in blood pressure homeostasis via S1P\u2010NO signaling and dissects the pathophysiological impact of endothelial\u2010derived S1P and ApoM of HDL\u2010bound S1P in hypertension and cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.021261","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T09:45:09Z","timestamp":1625823909000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine\u20101\u2010Phosphate"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6794-8291","authenticated-orcid":false,"given":"Ilaria","family":"Del Gaudio","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cardiovascular Research InstituteFeil Family Brain &amp; Mind Research InstituteWeill Cornell Medicine New York NY"},{"name":"Department of Obstetrics and Gynecology Medical University of Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Rubinelli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cardiovascular Research InstituteFeil Family Brain &amp; Mind Research InstituteWeill Cornell Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5298-2374","authenticated-orcid":false,"given":"Linda","family":"Sasset","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cardiovascular Research InstituteFeil Family Brain &amp; Mind Research InstituteWeill Cornell Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wadsack","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Medical University of Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-4065","authenticated-orcid":false,"given":"Timothy","family":"Hla","sequence":"additional","affiliation":[{"name":"Vascular Biology Program Boston Children's Hospital and Department of Surgery Harvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1239-4222","authenticated-orcid":false,"given":"Annarita","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cardiovascular Research InstituteFeil Family Brain &amp; Mind Research InstituteWeill Cornell Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1545"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76369"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.07.005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062411-130916"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R046300"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp086"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.233205"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81661-X"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10905"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12450"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008375200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009993200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09088"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02284"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610318200"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458509357065"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139221"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.165845"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14507"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60746"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038941"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3934"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85484"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-281956"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3520809"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103187108"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.RA119000277"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.08.071"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200418004"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00243"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1159\/000362993"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-010-0112-5"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-10-70"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2007.04.023"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04822.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500064"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2559"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw148"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.2001.5.2.89"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb14151.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1086\/687766"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201401-0121OC"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007931"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2017.12.005"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aal2722"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500064"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192616"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.307049"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.07.015"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep44131"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw256"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070657"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2010.12.001"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.114.302157"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052643"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.9811"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-019-0372-x"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801214200"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021817"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa2581"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2004.03.001"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/495349"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.607135"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00587.2006"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01331.2006"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003393"},{"key":"e_1_3_2_69_2","unstructured":"Guo Z Picataggi A Ripoll CV Chendamarai E Girardi A Riehl T Evie H Torrecilla JV Kovacs A Hyrc K et al. Apolipoprotein M attenuates doxorubicin cardiotoxicity by regulating transcription factor EB. bioRxiv. 2021:2021.2001.2012.426397."},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045323"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.021261","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:23:29Z","timestamp":1715599409000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.021261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":69,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2021,7,20]]}},"alternative-id":["10.1161\/JAHA.121.021261"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.021261","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]},"assertion":[{"value":"2021-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e021261"}}