{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:47:57Z","timestamp":1787496477900,"version":"build-2736575974"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["#2019\/12219-3"],"award-info":[{"award-number":["#2019\/12219-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["Process 446747\/2014-9"],"award-info":[{"award-number":["Process 446747\/2014-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["FAPEMIG-APQ-00760-18"],"award-info":[{"award-number":["FAPEMIG-APQ-00760-18"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    The vascular endothelium plays a pivotal role in the maintenance of vascular homeostasis, mediated by vasoactive molecules produced by endothelial cells. The balance between vasoconstrictor and vasodilator biomolecules is what guarantees this equilibrium. Therefore, an increase in the bioavailability of vasoconstrictors along with a reduction in vasodilators may indicate a condition known as endothelial dysfunction. Endothelial dysfunction is marked by an inflammatory process and reduced activity of vasoprotective enzymes, being characterized by some factors like the reduction of the bioavailability of nitric oxide (NO) and increase in the production of reactive oxygen species (ROS), pro-inflammatory and vasoconstrictor molecules. This condition is a predictive marker of several cardiovascular diseases (e.g., atherosclerosis, hypertension, and diabetes). Research is affected by the scarcity of suitable\n                    <jats:italic>in vitro<\/jats:italic>\n                    models that simulate endothelial dysfunction. The goal of this study was to induce an\n                    <jats:italic>in vitro<\/jats:italic>\n                    condition to mimic endothelial dysfunction by inhibiting NO synthesis in cells. Thymus-derived endothelial cells (tEnd.1) were treated with different concentrations of L-NAME (from 1 to 1,000\u00a0\u03bcM) for different times (12, 24, 48, 72, 96, and 120\u00a0h without and with retreatment every 24\u00a0h). Cell viability, nitrite concentration, p22\n                    <jats:sup>phox<\/jats:sup>\n                    , NOX2, NOX4, IL-6, and ACE genes expression and lipid peroxidation were evaluated. The results indicate that the treatment with 100\u00a0\u03bcM L-NAME for 72\u00a0h without retreatment reduced NO concentration and NOX4 gene expression while increasing ACE expression, thus mimicking reduced vascular protection and possibly increased vasoconstriction. On the other hand, treatment with 100\u00a0\u03bcM L-NAME for 96\u00a0h with retreatment reduced the concentration of NO and the expression of the p22\n                    <jats:sup>phox<\/jats:sup>\n                    gene while increasing the expression of the IL-6 and ACE genes, mimicking the increase in inflammation and vasoconstriction parameters. Based on these results, we thus propose that both 100\u00a0\u03bcM L-NAME for 72\u00a0h without retreatment and 100\u00a0\u03bcM L-NAME for 96\u00a0h with retreatment may be used as models for\n                    <jats:italic>in vitro<\/jats:italic>\n                    endothelial dysfunction according to the purpose of the study to be conducted.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2022.978378","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T14:13:17Z","timestamp":1668694397000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Endothelial dysfunction due to the inhibition of the synthesis of nitric oxide: Proposal and characterization of an in vitro cellular model"],"prefix":"10.3389","volume":"13","author":[{"given":"Fernanda Cardoso da","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Juber de","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina Santos","family":"Cordeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vin\u00edcius Marques","family":"Arruda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Quintanilha","family":"Faria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Ferreira Da Costa","family":"Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaise Gon\u00e7alves De","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Ribas","family":"F\u00fcrstenau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e20485","DOI":"10.7759\/cureus.20485","article-title":"The effects of L-arginine in hypertensive patients: A literature review","volume":"13","author":"Abukhodair","year":"2021","journal-title":"Cureus"},{"key":"B2","doi-asserted-by":"publisher","first-page":"L453","DOI":"10.1152\/ajplung.00393.2015","article-title":"Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities","volume":"311","author":"Aman","year":"2016","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"B3","first-page":"37","article-title":"Morte celular por apoptose: uma vis\u00e3o bioqu\u00edmica e molecular","volume":"1","author":"Anazetti","year":"2007","journal-title":"Metrocamp Pesqui."},{"key":"B4","doi-asserted-by":"publisher","first-page":"104224","DOI":"10.1016\/j.mvr.2021.104224","article-title":"Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis","volume":"138","author":"AndriantoAl-Farabi","year":"2021","journal-title":"Microvasc. Res."},{"key":"B5","first-page":"1386","article-title":"Regulation of nitric oxide synthesis in uraemia","volume":"10","author":"Arese","year":"1995","journal-title":"Nephrol. Dial. Transpl."},{"key":"B6","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1080\/713803730","article-title":"The NADPH oxidase of endothelial cells","volume":"50","author":"Babior","year":"2000","journal-title":"IUBMB life"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1182\/blood.v78.5.1262.bloodjournal7851262","article-title":"Endothelial cells express the interleukin-1 receptor type I","volume":"78","author":"Boraschi","year":"1991","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/s0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"52","author":"Buege","year":"1978","journal-title":"Methods Enzymol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/164_2020_390","article-title":"Tetrahydrobiopterin and nitric oxide synthase recouplers","volume":"264","author":"Channon","year":"2021","journal-title":"Handb. Exp. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"109485","DOI":"10.1016\/j.cellsig.2019.109485","article-title":"Endothelial tight junctions and their regulatory signaling pathways in vascular homeostasis and disease","volume":"66","author":"Cong","year":"2020","journal-title":"Cell. Signal."},{"key":"B11","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.ccc.2019.12.009","article-title":"Nitric oxide and endothelial dysfunction","volume":"36","author":"Cyr","year":"2020","journal-title":"Crit. Care Clin."},{"key":"B12","doi-asserted-by":"publisher","first-page":"E187","DOI":"10.3390\/ijms20010187","article-title":"New therapeutic implications of endothelial nitric oxide synthase (eNOS) function\/dysfunction in cardiovascular disease","volume":"20","author":"Daiber","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e20190745","DOI":"10.1084\/jem.20190745","article-title":"SIRT1-NOX4 signaling axis regulates cancer cachexia","volume":"217","author":"Dasgupta","year":"2020","journal-title":"J. Exp. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/sj.cdd.4400581","article-title":"Nitric oxide-an endothelial cell survival factor","volume":"6","author":"Dimmeler","year":"1999","journal-title":"Cell Death Differ."},{"key":"B15","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.tem.2014.06.012","article-title":"Endothelial NADPH oxidases: Which NOX to target in vascular disease?","volume":"25","author":"Drummond","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3088","DOI":"10.1172\/JCI97490","article-title":"Nox2 in regulatory T cells promotes angiotensin II-induced cardiovascular remodeling","volume":"128","author":"Emmerson","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B17","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1590\/s0104-42302000000300012","article-title":"Nitric oxide: The simple messenger passing through complexity. Metabolism, synthesis and functions","volume":"46","author":"Flora Filho","year":"2000","journal-title":"Rev. Assoc. Med. Bras."},{"key":"B18","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.lfs.2010.07.008","article-title":"L-NAME-treatment alters ectonucleotidase activities in kidney membranes of rats","volume":"87","author":"F\u00fcrstenau","year":"2010","journal-title":"Life Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1007\/s10557-021-07151-9","article-title":"Generation of a novel in vitro model to study endothelial dysfunction from atherothrombotic specimens","volume":"35","author":"Gallogly","year":"2021","journal-title":"Cardiovasc. Drugs Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1097\/fjc.0000000000001087","article-title":"Endothelium-dependent hyperpolarization: The evolution of myoendothelial microdomains","volume":"78","author":"Garland","year":"2021","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1084\/jem.181.1.9","article-title":"Middle T antigen-transformed endothelial cells exhibit an increased activity of nitric oxide synthase","volume":"181","author":"Ghigo","year":"1995","journal-title":"J. Exp. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1089\/jop.2000.16.121","article-title":"Glutathione: A vital lens antioxidant","volume":"16","author":"Giblin","year":"2000","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e12697","DOI":"10.14814\/phy2.12697","article-title":"Angiotensin II stimulates superoxide production by nitric oxide synthase in thick ascending limbs","volume":"4","author":"Gonzalez-Vicente","year":"2016","journal-title":"Physiol. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1477-7827-11-15","article-title":"L-Arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells","volume":"11","author":"Greene","year":"2013","journal-title":"Reprod. Biol. Endocrinol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"902","DOI":"10.2174\/1389450123666220303090413","article-title":"Oxidative stress: Meeting multiple targets in pathogenesis of vascular endothelial dysfunction","volume":"23","author":"Gupta","year":"2022","journal-title":"Curr. Drug Targets"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.3390\/cells10102712","article-title":"Vascular endothelial cells: Heterogeneity and targeting approaches","volume":"10","author":"Hennigs","year":"2021","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1177\/00220345211047510","article-title":"A pair of \"ACEs","volume":"101","author":"Hersh","year":"2022","journal-title":"J. Dent. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1016\/j.bbadis.2017.02.004","article-title":"Endothelial Nox4-based NADPH oxidase regulates atherosclerosis via soluble epoxide hydrolase","volume":"1863","author":"Hu","year":"2017","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"831847","DOI":"10.3389\/fcvm.2022.831847","article-title":"The induction of endothelial autophagy and its role in the development of atherosclerosis","volume":"9","author":"Hua","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.vph.2017.05.005","article-title":"Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases","volume":"100","author":"Incalza","year":"2018","journal-title":"Vasc. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00011-018-1129-8","article-title":"Vascular endothelium dysfunction: A conservative target in metabolic disorders","volume":"67","author":"Jamwal","year":"2018","journal-title":"Inflamm. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.3390\/life11121323","article-title":"Linking in vitro models of endothelial dysfunction with cell senescence","volume":"11","author":"Jimenez Trinidad","year":"2021","journal-title":"Life"},{"key":"B33","doi-asserted-by":"publisher","first-page":"H1626","DOI":"10.1152\/ajpheart.1996.271.4.H1626","article-title":"Expression of phagocyte NADPH oxidase components in human endothelial cells","volume":"271","author":"Jones","year":"1996","journal-title":"Am. J. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1038\/sj.bjp.0703665","article-title":"Endothelial nitric oxide synthase is a site of superoxide synthesis in endothelial cells treated with glyceryl trinitrate","volume":"131","author":"Kaesemeyer","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e13409","DOI":"10.14814\/phy2.13409","article-title":"A relative L-arginine deficiency contributes to endothelial dysfunction across the stages of the menopausal transition","volume":"5","author":"Klawitter","year":"2017","journal-title":"Physiol. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/s1734-1140(12)70846-0","article-title":"L-NAME in the cardiovascular system - nitric oxide synthase activator?","volume":"64","author":"Kopincov\u00e1","year":"2012","journal-title":"Pharmacol. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"E4411","DOI":"10.3390\/ijms20184411","article-title":"Vascular endothelial cell biology: An update","volume":"20","author":"Kr\u00fcger-Genge","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1093\/eurheartj\/ehv564","article-title":"NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice","volume":"37","author":"Langbein","year":"2016","journal-title":"Eur. Heart J."},{"key":"B39","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.freeradbiomed.2017.12.017","article-title":"NADPH oxidase 4 and endothelial nitric oxide synthase contribute to endothelial dysfunction mediated by histone methylations in metabolic memory","volume":"115","author":"Liao","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cellsig.2005.03.023","article-title":"Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases","volume":"18","author":"Martyn","year":"2006","journal-title":"Cell. Signal."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1172\/jci10506","article-title":"Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice","volume":"106","author":"Matoba","year":"2000","journal-title":"J. Clin. Invest."},{"key":"B42","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/cvr\/cvx252","article-title":"Cardiovascular protection by Nox4","volume":"114","author":"Morawietz","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1097\/hjh.0000000000000965","article-title":"Endothelial dysfunction in human essential hypertension","volume":"34","author":"Mordi","year":"2016","journal-title":"J. Hypertens."},{"key":"B44","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"B45","doi-asserted-by":"publisher","first-page":"E2852","DOI":"10.3390\/ijms20122852","article-title":"New insights into the role of polybromo-1 in prostate cancer","volume":"20","author":"Mota","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1021\/bi9022285","article-title":"Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain","volume":"49","author":"Nisimoto","year":"2010","journal-title":"Biochemistry"},{"key":"B47","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/0006-291x(92)91266-s","article-title":"The non specificity of specific nitric oxide synthase inhibitors","volume":"187","author":"Peterson","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1111\/j.1476-5381.1996.tb15557.x","article-title":"Inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME): Requirement for bioactivation to the free acid, NG-nitro-L-arginine","volume":"118","author":"Pfeiffer","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1177\/0003319717732238","article-title":"Endothelial dysfunction and venous thrombosis","volume":"69","author":"Poredos","year":"2018","journal-title":"Angiology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1161\/atvbaha.110.219238","article-title":"Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo","volume":"31","author":"Ray","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1111\/j.1476-5381.1990.tb14151.x","article-title":"Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo","volume":"101","author":"Rees","year":"1990","journal-title":"Br. J. Pharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"112398","DOI":"10.1016\/j.yexcr.2020.112398","article-title":"The role of vascular niche and endothelial cells in organogenesis and regeneration","volume":"398","author":"Ribatti","year":"2021","journal-title":"Exp. Cell Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1086\/302304","article-title":"Nitric oxide in endothelial dysfunction and vascular remodeling: Clinical correlates and experimental links","volume":"64","author":"Rudic","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1016\/j.bbadis.2013.08.006","article-title":"Endothelial dysfunction - a major mediator of diabetic vascular disease","volume":"1832","author":"Sena","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B55","doi-asserted-by":"publisher","first-page":"105","DOI":"10.31083\/j.fbl2703105","article-title":"Oxidative stress-induced endothelial dysfunction in cardiovascular diseases","volume":"27","author":"Shaito","year":"2022","journal-title":"Front. Biosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1007\/s00125-004-1525-1","article-title":"Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells","volume":"47","author":"Srinivasan","year":"2004","journal-title":"Diabetologia"},{"key":"B57","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/978-3-319-57613-8_4","article-title":"Endothelial cells","volume":"1003","author":"Sturtzel","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2607","DOI":"10.1161\/01.cir.0000066909.13953.f1","article-title":"Critical role of L-arginine in endothelial cell survival during oxidative stress","volume":"107","author":"Suschek","year":"2003","journal-title":"Circulation"},{"key":"B59","doi-asserted-by":"publisher","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"4","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.bbrc.2019.04.128","article-title":"p22phox promotes Ang-II-induced vascular smooth muscle cell phenotypic switch by regulating KLF4 expression","volume":"514","author":"Tang","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B61","doi-asserted-by":"publisher","first-page":"781","DOI":"10.3390\/biomedicines9070781","article-title":"Inflammatory mechanisms contributing to endothelial dysfunction","volume":"9","author":"Theofilis","year":"2021","journal-title":"Biomedicines"},{"key":"B62","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.bbrc.2017.01.132","article-title":"Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid","volume":"484","author":"Tian","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B63","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1007\/978-1-4939-6625-7_28","article-title":"Evaluation of endothelial dysfunction in vivo","volume":"1527","author":"Todiras","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/apha.12646","article-title":"Endothelial dysfunction and vascular disease - a 30th anniversary update","volume":"219","author":"Vanhoutte","year":"2017","journal-title":"Acta Physiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1748-1716.2009.01964.x","article-title":"Endothelial dysfunction and vascular disease","volume":"196","author":"Vanhoutte","year":"2009","journal-title":"Acta Physiol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.resp.2014.12.012","article-title":"Endothelial nitric oxide synthase uncoupling: A novel pathway in OSA induced vascular endothelial dysfunction","volume":"207","author":"Varadharaj","year":"2015","journal-title":"Respir. Physiol. Neurobiol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1080\/14728222.2021.1988928","article-title":"Endothelial dysfunction: A therapeutic target in bacterial sepsis?","volume":"25","author":"Vincent","year":"2021","journal-title":"Expert Opin. Ther. Targets"},{"key":"B68","doi-asserted-by":"publisher","first-page":"318087","DOI":"10.1155\/2012\/318087","article-title":"Arginine-based inhibitors of nitric oxide synthase: Therapeutic potential and challenges","volume":"2012","author":"V\u00edte\u010dek","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"B69","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0092-8674(88)90536-3","article-title":"Embryonic lethalities and endothelial tumors in chimeric mice expressing polyoma virus middle T oncogene","volume":"52","author":"Williams","year":"1988","journal-title":"Cell"},{"key":"B70","doi-asserted-by":"publisher","first-page":"25804","DOI":"10.1074\/jbc.273.40.25804","article-title":"Superoxide generation from endothelial nitric-oxide synthase. A Ca2+\/calmodulin-dependent and tetrahydrobiopterin regulatory process","volume":"273","author":"Xia","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1124\/pharmrev.120.000096","article-title":"Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: From mechanism to pharmacotherapies","volume":"73","author":"Xu","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"B72","doi-asserted-by":"publisher","first-page":"6813016","DOI":"10.1155\/2016\/6813016","article-title":"Endothelial dysfunction and inflammation: Immunity in rheumatoid arthritis","volume":"2016","author":"Yang","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"B73","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.mvr.2018.03.012","article-title":"Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy?","volume":"119","author":"Yuyun","year":"2018","journal-title":"Microvasc. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41569-019-0260-8","article-title":"NADPH oxidases and oxidase crosstalk in cardiovascular diseases: Novel therapeutic targets","volume":"17","author":"Zhang","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1172\/jci117557","article-title":"Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P","volume":"94","author":"Ziche","year":"1994","journal-title":"J. Clin. Invest."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.978378\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T14:13:23Z","timestamp":1668694403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.978378\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":75,"alternative-id":["10.3389\/fphys.2022.978378"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.978378","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,17]]},"article-number":"978378"}}