{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:53:43Z","timestamp":1787921623211,"version":"build-2784847793"},"reference-count":43,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2020,10,10]],"date-time":"2020-10-10T00:00:00Z","timestamp":1602288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Cardiovascular Diseases and Sciences (CCDS), LSUHSC-Shreveport","award":["Malcolm W. Feist Cardiovascular Research Fellowship to Rajesh Parsanathan"],"award-info":[{"award-number":["Malcolm W. Feist Cardiovascular Research Fellowship to Rajesh Parsanathan"]}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["RO1 AT007442, 2013-16"],"award-info":[{"award-number":["RO1 AT007442, 2013-16"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["1 R33 AT010637-01A1, 2020-2023"],"award-info":[{"award-number":["1 R33 AT010637-01A1, 2020-2023"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic inherited trait among humans, affects ~7% of the global population, and is associated with excess risk of cardiovascular disease (CVD). Transforming growth factor-\u03b2 (TGF-\u03b2) regulates immune function, proliferation, epithelial-mesenchymal transition, fibrosis, cancer, and vascular dysfunction. This study examined whether G6PD deficiencies can alter TGF-\u03b2-mediated NADPH oxidases (NOX) and cell adhesion molecules (CAM) in human aortic endothelial cells (HAEC). Results show that treatment with high glucose and the saturated free fatty acid palmitate significantly downregulated G6PD; in contrast, mRNA levels of TGF-\u03b2 components, NOX and its activity, and reactive oxygen species (ROS) were significantly upregulated in HAEC. The expression levels of TGF-\u03b2 and its receptors, NOX and its activity, and ROS were significantly higher in HG-exposed G6PD-deficient cells (G6PD siRNA) compared to G6PD-normal cells. The protein levels of adhesion molecules (ICAM-1 and VCAM-1) and inflammatory cytokines (MCP-1 and TNF) were significantly increased in HG-exposed G6PD-deficient cells compared to G6PD-normal cells. The adherence of monocytes (SC cells) to HAEC was significantly elevated in HG-treated G6PD-deficient cells compared to control cells. Pharmacological inhibition of G6PD enhances ROS, NOX and its activity, and endothelial monocyte adhesion; these effects were impeded by NOX inhibitors. The inhibition of TGF-\u03b2 prevents NOX2 and NOX4 mRNA expression and activity, ROS, and adhesion of monocytes to HAEC. L-Cysteine ethyl ester (cell-permeable) suppresses the mRNA levels of TGF-\u03b2 and its receptors, along with NOX2 and NOX4, and decreases NOX activity, ROS, and adhesion of monocytes to HAEC. This suggests that G6PD deficiency promotes TGF-\u03b2\/NADPH oxidases\/ROS signaling, the expression of ICAM-1 and VCAM-1, and the adhesion of leukocytes to the endothelial monolayer, which can contribute to a higher risk for CVD.<\/jats:p>","DOI":"10.3390\/ijms21207474","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T22:02:02Z","timestamp":1602626522000},"page":"7474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Glucose-6-Phosphate Dehydrogenase Deficiency Activates Endothelial Cell and Leukocyte Adhesion Mediated via the TGF\u03b2\/NADPH Oxidases\/ROS Signaling Pathway"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-3507","authenticated-orcid":false,"given":"Rajesh","family":"Parsanathan","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-0436","authenticated-orcid":false,"given":"Sushil K.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0957-5839(95)80223-1","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"5","author":"Layton","year":"1995","journal-title":"Curr. 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