{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:41:03Z","timestamp":1787902863710,"version":"build-2784847793"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada","award":["# RGPIN 06611-2018"],"award-info":[{"award-number":["# RGPIN 06611-2018"]}]},{"name":"University of Saskatchewan","award":["# RGPIN 06611-2018"],"award-info":[{"award-number":["# RGPIN 06611-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Nitric oxide (NO), synthesized by endothelial nitric oxide synthase (eNOS), plays a critical role in blood pressure regulation. Genome-wide association studies have identified genetic susceptibility loci for hypertension in human lymphocyte-specific protein 1 (LSP1) gene. LSP1 is recognized as modulator of leukocyte extravasation, and endothelial permeability, however, the role of LSP1 in regulation of NO signaling within endothelial cells (ECs) remains unknown. The present study investigated the role of LSP1 in the regulation of eNOS expression and activity utilizing human macrovascular ECs in vitro and LSP1 knockout (KO) mice. In ECs, specific CRISPR-Cas9 genomic editing deleted LSP1 and caused downregulation of eNOS expression. LSP1 gain-of-function through adenovirus-mediated gene transfer was associated with enhanced expression of eNOS. Co-immunoprecipitation and confocal fluorescence microscopy revealed that eNOS and LSP1 formed a protein complex under basal conditions in ECs. Furthermore, LSP1 deficiency in mice promoted significant upregulation and instability of eNOS. Utilizing a mass-spectrometry-based bottom-up proteomics approach, we identified novel truncated forms of eNOS in immunoprecipitates from LSP1 KO aortae. Our experimental data suggest an important role of endothelial LSP1 in regulation of eNOS expression and activity within human ECs and murine vascular tissues.<\/jats:p>","DOI":"10.3390\/biom14010111","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T11:15:01Z","timestamp":1705317301000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lymphocyte-Specific Protein 1 Regulates Expression and Stability of Endothelial Nitric Oxide Synthase"],"prefix":"10.3390","volume":"14","author":[{"given":"Musstafa","family":"Smeir","sequence":"first","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulos","family":"Chumala","sequence":"additional","affiliation":[{"name":"Department of Medicine, Canadian Center for Rural and Agricultural Health, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0869-7300","authenticated-orcid":false,"given":"George S.","family":"Katselis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Canadian Center for Rural and Agricultural Health, University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"III27","DOI":"10.1161\/01.CIR.0000131515.03336.f8","article-title":"Role of endothelial dysfunction in atherosclerosis","volume":"109","author":"Davignon","year":"2004","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jvs.2004.03.043","article-title":"Nitric oxide and arterial disease","volume":"40","author":"Barbato","year":"2004","journal-title":"J. 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