{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:57:55Z","timestamp":1790866675091,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007686","name":"Instituto Nacional de Perinatologia","doi-asserted-by":"publisher","award":["2017-3-118"],"award-info":[{"award-number":["2017-3-118"]}],"id":[{"id":"10.13039\/501100007686","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2017-3-118"],"award-info":[{"award-number":["2017-3-118"]}],"id":[{"id":"https:\/\/ror.org\/00ctdh943","id-type":"ROR","asserted-by":"publisher"}]},{"name":"FOSISS-CONACyT","award":["S0008-2017-1-290060"],"award-info":[{"award-number":["S0008-2017-1-290060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Endothelial dysfunction is a hallmark of vascular injury and a central event in cardiovascular and inflammatory diseases. It is characterized by reduced nitric oxide (NO) bioavailability, increased oxidative stress, and disruption of endothelial barrier integrity. Activated neutrophils contribute to this process through the generation of reactive oxygen species and other oxidative mediators. Here, we investigated whether L-arginine, the principal substrate for endothelial NO synthase (eNOS), attenuates neutrophil-induced endothelial injury. Primary human umbilical vein endothelial cells (HUVECs) were exposed to sustained L-arginine supplementation initiated at passage 1 and subsequently challenged with activated neutrophils. Neutrophil exposure reduced stable NO metabolites (NOx), decreased eNOS phosphorylation at Ser1177, increased oxidant-sensitive DCF fluorescence, induced oxidative damage to lipids, proteins, and nucleic acids, disrupted PECAM-1\/CD31-associated junctional organization, and increased endothelial permeability. Sustained L-arginine supplementation increased NOx accumulation in neutrophil-exposed cultures, partially preserved eNOS Ser1177 phosphorylation, attenuated oxidative damage, and improved endothelial barrier integrity. Catalase reduced oxidant-sensitive fluorescence and permeability, supporting a ROS-dependent component of the injury model. Targeted PCR array analysis identified neutrophil-associated changes in oxidative stress-related gene-expression patterns; however, direct comparison between L-arginine-supplemented and non-supplemented neutrophil-exposed cultures showed no statistically significant gene-expression changes after Benjamini\u2013Hochberg FDR correction. These findings indicate that L-arginine attenuates neutrophil-induced endothelial injury primarily through biochemical, functional, and structural mechanisms, whereas transcriptional findings should be interpreted as exploratory and hypothesis-generating. Additional studies are required to determine the translational relevance of L-arginine supplementation as a potential approach to preserve endothelial function under oxidative and inflammatory stress.<\/jats:p>","DOI":"10.3390\/ijms27188347","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:23:56Z","timestamp":1790864636000},"page":"8347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["L-Arginine Mitigates Neutrophil-Induced Endothelial Injury by Preserving Nitric Oxide Signaling and Redox Homeostasis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9087-8017","authenticated-orcid":false,"given":"Aurora","family":"Espejel-Nu\u00f1ez","sequence":"first","affiliation":[{"name":"Immunobiochemistry Department, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico"},{"name":"Postgraduate in Experimental Biology, Division of Biological and Health Sciences, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09310, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-6098","authenticated-orcid":false,"given":"Arturo","family":"Flores-Pliego","sequence":"additional","affiliation":[{"name":"Immunobiochemistry Department, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico"},{"name":"Postgraduate in Experimental Biology, Division of Biological and Health Sciences, Universidad Aut\u00f3noma Metropolitana-Iztapalapa, Mexico City 09310, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7276-8463","authenticated-orcid":false,"given":"Salvador Espino","family":"y Sosa","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-4133","authenticated-orcid":false,"given":"Johnatan","family":"Torres-Torres","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatolog\u00eda, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-3857","authenticated-orcid":false,"given":"Raigam Jafet","family":"Martinez-Portilla","sequence":"additional","affiliation":[{"name":"Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7701-9621","authenticated-orcid":false,"given":"Hector","family":"Borboa-Olivares","sequence":"additional","affiliation":[{"name":"Clinical Research Branch, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-2793","authenticated-orcid":false,"given":"Araceli","family":"Montoya-Estrada","sequence":"additional","affiliation":[{"name":"Coordination of Gynecological and Perinatal Endocrinology, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3699-8633","authenticated-orcid":false,"given":"Aar\u00f3n","family":"Galindo-Vega","sequence":"additional","affiliation":[{"name":"Functional Genomics of Cancer Laboratory, Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-5228","authenticated-orcid":false,"given":"Sandra","family":"Parra-Hernandez","sequence":"additional","affiliation":[{"name":"Immunobiochemistry Department, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Ismael","family":"Mancilla-Herrera","sequence":"additional","affiliation":[{"name":"Biomedical Research Branch, Instituto Nacional de 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