{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:08:47Z","timestamp":1787062127231,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Tetralogy of Fallot (ToF) is a cyanotic congenital heart disease, composed of four malformations: persistent communication between the right and the left ventricle, pulmonary stenosis, overriding aorta, and right ventricle hypertrophy. The etiology of this disease is not entirely known as yet, but it has been proposed that the pathology has genetic components. During embryonic development, the fetus is exposed to a physiological hypoxia to facilitate the formation of blood vessels and blood cells through\n                      <jats:italic>de novo<\/jats:italic>\n                      processes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After researching scientific databases on the implications of oxygen on the normal and abnormal development of organs, especially the heart, we were able to propose that oxygen deprivation may be the cause of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During this period, the hypoxia\u2010inducible factor is activated and triggers transcriptional responses that enable adaptation to the hypoxic environment through angiogenic activation. High levels of this protein can alter certain physiological pathways, such as those related to the vascular endothelial growth factor. Research has shown that prolonged oxygen deprivation during embryological development can lead to the occurrence of congenital heart diseases, such as ToF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Studies using animal models have demonstrated that the deficiency or disruption of a protein called \u201cCITED2,\u201d which plays an important role in cardiac morphogenesis and its loss, results in the alteration of pluripotent, cardiac, and neural lineage differentiation, thereby disrupting the normal development of the heart and other tissues.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bdr2.2279","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T13:06:25Z","timestamp":1705496785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tetralogy of\n                    <scp>Fallot<\/scp>\n                    : Hypoxia, the villain of the story?"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-3778","authenticated-orcid":false,"given":"Carlos Ariel","family":"Boj\u00f3rquez Mart\u00ednez","sequence":"first","affiliation":[{"name":"Faculty of Medicine Facultad Mexicana de Medicina\u2014La Salle University  Mexico City Tlalpan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid Montserrat","family":"Garc\u00eda Murillo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Facultad Mexicana de Medicina\u2014La Salle University  Mexico City Tlalpan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Seg\u00f3n Mora","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Facultad Mexicana de Medicina\u2014La Salle University  Mexico City Tlalpan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-390X","authenticated-orcid":false,"given":"Andrea","family":"L\u00f3pez Mereles","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Facultad Mexicana de Medicina\u2014La Salle University  Mexico City Tlalpan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","unstructured":"An B. 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