{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:49:31Z","timestamp":1765039771071,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Department of Veterans Affairs Biomedical Laboratory R&amp;D Service","award":["I01 BX003482","BX005993-01","5T32 GM108554"],"award-info":[{"award-number":["I01 BX003482","BX005993-01","5T32 GM108554"]}]},{"name":"National Institutes of Health","award":["I01 BX003482","BX005993-01","5T32 GM108554"],"award-info":[{"award-number":["I01 BX003482","BX005993-01","5T32 GM108554"]}]},{"name":"Society of Cardiovascular Anesthesiologists","award":["I01 BX003482","BX005993-01","5T32 GM108554"],"award-info":[{"award-number":["I01 BX003482","BX005993-01","5T32 GM108554"]}]},{"name":"Foundation of Anesthesia Education and Research","award":["I01 BX003482","BX005993-01","5T32 GM108554"],"award-info":[{"award-number":["I01 BX003482","BX005993-01","5T32 GM108554"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Poloxamer (P) 188 attenuates myocardial ischemia\/reperfusion injury through cell membrane stabilization. Cell\u2013cell interactions between endothelial cells (ECs) and cardiomyocytes (CMs) further protect CMs: co-cultures showed that, at an optimal density, ECs protected CMs against hypoxia\/reoxygenation (HR) injury. The mechanism of interaction with P188 still requires exploration. We examined if N(\u03c9)-nitro-L-arginine methyl ester (LNAME), a non-specific nitric oxide (NO) synthase inhibitor, abolishes protection in the presence or absence of P188 and\/or ECs. We co-cultured mouse coronary artery ECs in an insert atop mouse CMs plated at confluency on the bottom of a well. Normoxic controls remained in complete media while HR groups were exposed to 24 h hypoxia at 0.01% O2 in serum- and glucose-free media, followed by 2 h reoxygenation in complete media. P188 (300 \u03bcM), LNAME (40 mM), or vehicle were administered upon reoxygenation. ECs at the used lower density did not decrease HR-triggered lactate dehydrogenase release or calcium overload in CMs by themselves. P188 reduced both indicators after HR by 16\/18% without and by 22\/25% with ECs, respectively. LNAME abrogated CM protection by P188. Neither intervention had an effect under normoxia. Our co-culture data indicates that P188 requires NO, not necessarily of endothelial origin, to elicit CM protection.<\/jats:p>","DOI":"10.3390\/cells14131001","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T11:37:51Z","timestamp":1751283471000},"page":"1001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Nitric Oxide in Cardioprotection by Poloxamer 188"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-8845","authenticated-orcid":false,"given":"Zhu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3313-3112","authenticated-orcid":false,"given":"Matthew B.","family":"Barajas","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Anesthesiology, TVHS VA Medical Center, Nashville, TN 37212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-6836","authenticated-orcid":false,"given":"Takuro","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-5757","authenticated-orcid":false,"given":"Matthias L.","family":"Riess","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"},{"name":"Department of Anesthesiology, TVHS VA Medical Center, Nashville, TN 37212, USA"},{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1096\/fasebj.5.7.2010056","article-title":"Role of endothelial dysfunction in the pathogenesis of reperfusion injury after myocardial ischemia","volume":"5","author":"Lefer","year":"1991","journal-title":"FASEB J."},{"key":"ref_2","first-page":"265","article-title":"Endothelial dysfunction and reactive oxygen species production in ischemia\/reperfusion and nitrate tolerance","volume":"23","author":"Szocs","year":"2004","journal-title":"Gen. 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