{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T11:04:28Z","timestamp":1769857468615,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Heart Association","award":["850700\/21"],"award-info":[{"award-number":["850700\/21"]}]},{"name":"American Heart Association","award":["HL60190"],"award-info":[{"award-number":["HL60190"]}]},{"name":"American Heart Association","award":["HL137282"],"award-info":[{"award-number":["HL137282"]}]},{"name":"American Heart Association","award":["HL134610"],"award-info":[{"award-number":["HL134610"]}]},{"name":"American Heart Association","award":["HL142212"],"award-info":[{"award-number":["HL142212"]}]},{"name":"American Heart Association","award":["HL146369"],"award-info":[{"award-number":["HL146369"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endothelial glycocalyx is a dynamic signaling surface layer that is involved in the maintenance of cellular homeostasis. The glycocalyx has a very diverse composition, with glycoproteins, proteoglycans, and glycosaminoglycans interacting with each other to form a mesh-like structure. Due to its highly interactive nature, little is known about the relative contribution of each glycocalyx constituent to its overall function. Investigating the individual roles of the glycocalyx components to cellular functions and system physiology is challenging, as the genetic manipulation of animals that target specific glycocalyx components may result in the development of a modified glycocalyx. Thus, it is crucial that genetically modified animal models for glycocalyx components are characterized and validated before the development of mechanistic studies. Among the glycocalyx components, glypican 1, which acts through eNOS-dependent mechanisms, has recently emerged as a player in cardiovascular diseases. Whether glypican 1 regulates eNOS in physiological conditions is unclear. Herein, we assessed how the deletion of glypican 1 affects the development of the pulmonary endothelial glycocalyx and the impact on eNOS activity and endothelial function. Male and female 5\u20139-week-old wild-type and glypican 1 knockout mice were used. Transmission electron microscopy, immunofluorescence, and immunoblotting assessed the glycocalyx structure and composition. eNOS activation and content were assessed by immunoblotting; nitric oxide production was assessed by the Griess reaction. The pulmonary phenotype was evaluated by histological signs of lung injury, in vivo measurement of lung mechanics, and pulmonary ventilation. Glypican 1 knockout mice showed a modified glycocalyx with increased glycocalyx thickness and heparan sulfate content and decreased expression of syndecan 4. These alterations were associated with decreased phosphorylation of eNOS at S1177. The production of nitric oxides was not affected by the deletion of glypican 1, and the endothelial barrier was preserved in glypican 1 knockout mice. Pulmonary compliance was decreased, and pulmonary ventilation was unaltered in glypican 1 knockout mice. Collectively, these data indicate that the deletion of glypican 1 may result in the modification of the glycocalyx without affecting basal lung endothelial function, validating this mouse model as a tool for mechanistic studies that investigate the role of glypican 1 in lung endothelial function.<\/jats:p>","DOI":"10.3390\/ijms241914568","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:55:01Z","timestamp":1695718501000},"page":"14568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Pulmonary Endothelial Glycocalyx Modifications in Glypican 1 Knockout Mice Do Not Affect Lung Endothelial Function in Physiological Conditions"],"prefix":"10.3390","volume":"24","author":[{"given":"Lakshmi N. R.","family":"Thota","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, College of Medicine-Tucson, The University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8435-672X","authenticated-orcid":false,"given":"Joaquin E.","family":"Lopez Rosales","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, College of Medicine-Tucson, The University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Placencia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, College of Medicine-Tucson, The University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny A.","family":"Zemskov","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA"},{"name":"Department of Cellular Biology & Pharmacology, Howard Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2482-3461","authenticated-orcid":false,"given":"Paola","family":"Tonino","sequence":"additional","affiliation":[{"name":"Research, Innovation & Impact Cores Facilities, Imaging Cores-Electron, Life Sciences North, The University of Arizona, Tucson, AZ 85719, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley N.","family":"Michael","sequence":"additional","affiliation":[{"name":"Asthma and Airway Disease Research Center, The University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M.","family":"Black","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA"},{"name":"Department of Cellular Biology & Pharmacology, Howard Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA"},{"name":"Department of Environmental Health Sciences, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33174, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia Z.","family":"Chignalia","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, College of Medicine-Tucson, The University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Physiology, College of Medicine-Tucson, The University of Arizona, Tucson, AZ 85724, USA"},{"name":"Sarver Heart Center, The University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/bs.ctm.2023.02.004","article-title":"Setting the stage for universal pharmacological targeting of the glycocalyx","volume":"91","author":"Almahayni","year":"2023","journal-title":"Curr. 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