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ROS signaling regulates gene expression, cell proliferation, apoptosis, and migration. However, the role of NOX2 in embryonic heart development remains elusive. We hypothesized that deficiency of <jats:italic>Nox2<\/jats:italic> disrupts endocardial to mesenchymal transition (EndMT) and results in congenital septal and valvular defects. Our data show that 34% of <jats:italic>Nox2<jats:sup>-\/-<\/jats:sup><\/jats:italic> neonatal mice had various congenital heart defects (CHDs) including atrial septal defects (ASD), ventricular septal defects (VSD), atrioventricular canal defects (AVCD), and malformation of atrioventricular and aortic valves. Notably, <jats:italic>Nox2<jats:sup>-\/-<\/jats:sup><\/jats:italic> embryonic hearts show abnormal development of the endocardial cushion as evidenced by decreased cell proliferation and an increased rate of apoptosis. Additionally, <jats:italic>Nox2<\/jats:italic> deficiency disrupted EndMT of atrioventricular cushion explants <jats:italic>ex vivo<\/jats:italic>. Furthermore, treatment with N-acetylcysteine (NAC) to reduce ROS levels in the wild-type endocardial cushion explants decreased the number of cells undergoing EndMT. Importantly, deficiency of <jats:italic>Nox2<\/jats:italic> was associated with reduced expression of <jats:italic>Gata4<\/jats:italic>, <jats:italic>Tgf\u03b22<\/jats:italic>, <jats:italic>Bmp2<\/jats:italic>, <jats:italic>Bmp4<\/jats:italic>, and <jats:italic>Snail1<\/jats:italic>, which are critical to endocardial cushion and valvoseptal development. We conclude that NOX2 is critical to EndMT, endocardial cushion cell proliferation, and normal embryonic heart development.<\/jats:p>","DOI":"10.1155\/2020\/1679045","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T23:30:42Z","timestamp":1592523042000},"page":"1-12","source":"Crossref","is-referenced-by-count":15,"title":["NOX2 Is Critical to Endocardial to Mesenchymal Transition and Heart Development"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8607-6545","authenticated-orcid":true,"given":"Hoda","family":"Moazzen","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Canada"},{"name":"Institute of Molecular and Cellular Anatomy, Medical Faculty, Wendlingweg 2 RWTH Aachen University, Aachen, 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