L-Arginine Mitigates Neutrophil-Induced Endothelial Injury by Preserving Nitric Oxide Signaling and Redox Homeostasis
10 affiliations
- 1Immunobiochemistry Department, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico
- 2Postgraduate in Experimental Biology, Division of Biological and Health Sciences, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09310, Mexico
- 3Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatología, Mexico City 11000, Mexico
- 4Iberoamerican Research Network in Obstetrics, Gynecology and Translational Medicine, Mexico City, Mexico
- 5Clinical Research Branch, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico
- 6Coordination of Gynecological and Perinatal Endocrinology, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico
- 7Functional Genomics of Cancer Laboratory, Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico
- 8Biomedical Research Branch, Instituto Nacional de Perinatologia, Mexico City 11000, Mexico
- 9Department of Electrical Engineering, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Mexico City 09310, Mexico
- 10Department of Health Sciences, Universidad Autónoma Metropolitana, Unidad Iztapalapa, Mexico City 09310, Mexico
Abstract
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–Hochberg 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.
Related
- H3K18la- driven neutrophil secretory autophagy promotes pulmonary endothelial dysfunction in sepsis-induced lung injury
- Endothelial KLK10 maintains blood-brain barrier integrity and mitigates ischemic stroke by limiting the cGAS-STING pathway.
- Cyanidin-3-O-Glucoside in Anthocyanin-Rich Fraction Combined with Atorvastatin Mitigates Kidney Injury via Attenuating Renal Lipotoxicity and Oxidative Stress and Preserving Mitochondrial Function in Obese Rats
- Lymphatic endothelial cells regulate neutrophil phenotypes and function in a microphysiological model of infection
- Neutrophil-derived oncostatin m contributes to endothelial cell dysfunction during Treponema denticola interaction
BibTeX
@article{espejelnunez2026larginine,
title = {{L-Arginine Mitigates Neutrophil-Induced Endothelial Injury by Preserving Nitric Oxide Signaling and Redox Homeostasis}},
author = {Aurora Espejel-Nuñez and Arturo Flores-Pliego and Salvador Espino y Sosa and Johnatan Torres-Torres and Raigam Jafet Martinez-Portilla and Hector Borboa-Olivares and Araceli Montoya-Estrada and Aarón Galindo-Vega and Sandra Parra-Hernandez and Ismael Mancilla-Herrera and Juan Carlos Echeverria-Arjonilla and Ramon Gonzalez-Camarena and Guadalupe Estrada-Gutierrez},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27188347},
url = {https://www.mdpi.com/1422-0067/27/18/8347},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - L-Arginine Mitigates Neutrophil-Induced Endothelial Injury by Preserving Nitric Oxide Signaling and Redox Homeostasis
AU - Aurora Espejel-Nuñez
AU - Arturo Flores-Pliego
AU - Salvador Espino y Sosa
AU - Johnatan Torres-Torres
AU - Raigam Jafet Martinez-Portilla
AU - Hector Borboa-Olivares
AU - Araceli Montoya-Estrada
AU - Aarón Galindo-Vega
AU - Sandra Parra-Hernandez
AU - Ismael Mancilla-Herrera
AU - Juan Carlos Echeverria-Arjonilla
AU - Ramon Gonzalez-Camarena
AU - Guadalupe Estrada-Gutierrez
PY - 2026
DA - 2026/09/19
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27188347
UR - https://www.mdpi.com/1422-0067/27/18/8347
AB - 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–Hochberg 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.
SN - 1422-0067
ER -