{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:33:18Z","timestamp":1761802398046,"version":"build-2065373602"},"reference-count":78,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM145379"],"award-info":[{"award-number":["R35GM145379"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Microvascular hyperpermeability is a serious complication that occurs from hemorrhagic shock and resuscitation (HSR), especially when combined with acute alcohol intoxication (AAI). We tested the hypothesis that administration of Apolipoprotein M (ApoM), a lipocalin that normally resides in plasma high\u2010density lipoproteins (HDL) and a carrier of sphingosine\u20101\u2010phosphate (S1P), reduces combined AAI and HSR\u2010induced microvascular leakage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An established rat model of AAI\/HSR was combined with intravital microscopy to study whether the administration of ApoM in resuscitative fluids reduces microvascular leakage of FITC\u2010albumin. The impact of ApoM on human umbilical vein endothelial cell (HUVEC) monolayer barrier function and junctional integrity was tested, using trans\u2010endothelial electrical resistance (TER) and immunofluorescence labeling of junctional VE\u2010Cadherin, respectively. Immunoprecipitation of ApoM in HUVEC and mass spectrometry of complexes were used to determine potential binding partners. The Rac1 G\u2010LISA assay was used to determine if ApoM causes Rac1 activation in HUVEC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to sham controls, combined AAI and HSR significantly increased microvascular leakage. Administration of S1P, ApoM, or their combination during resuscitation significantly decreased microvascular leakage. In HUVEC monolayers, with or without alcohol pretreatment, S1P, ApoM, and S1P\u2009+\u2009ApoM all significantly increased barrier function and improved the junctional integrity of VE\u2010cadherin compromised by alcohol. The small GTPase Rac1 was found to bind with ApoM in HUVEC and was significantly activated within 5\u2009min of ApoM addition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The findings suggest that fluid resuscitation with ApoM ameliorates AAI\/HSR\u2010induced microvascular leakage. The mechanism involves stabilizing VE\u2010Cadherin junction integrity, which could be caused by Rac1 activation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/micc.70030","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:14Z","timestamp":1760120054000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Apolipoprotein M (\n                    <scp>ApoM<\/scp>\n                    ) Ameliorates Acute Alcohol Intoxication (\n                    <scp>AAI<\/scp>\n                    )\u2010Hemorrhagic Shock and Resuscitation (\n                    <scp>HSR<\/scp>\n                    )\u2010Induced Microvascular Leakage"],"prefix":"10.1111","volume":"32","author":[{"given":"Mengmeng","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine University of South Florida  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-3151","authenticated-orcid":false,"given":"Jerome W.","family":"Breslin","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology, Morsani College of Medicine University of South Florida  Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.08.052290"},{"volume-title":"Injuries and 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