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The EF5\u2010positive tissues were also specifically positive for nuclear\u2010localized hypoxia inducible factor\u20101 alpha (HIF\u20101\u03b1), the oxygen\u2010sensitive component of the hypoxia inducible factor\u20101 (HIF\u20101) heterodimer. This led to our hypothesis that there is a \u201ctemplate\u201d of hypoxic tissue that determines the stereotyped pattern of the major coronary vessels. In this study, we disturbed this template by altering ambient oxygen levels (hypoxia 15%; hyperoxia 75\u201340%) during the early phases of avian coronary vessel development, in order to alter tissue hypoxia, HIF\u20101\u03b1 protein expression, and its downstream target genes without high mortality. We also altered HIF\u20101\u03b1 gene expression in the embryonic outflow tract cardiomyocytes by injecting an adenovirus containing a constitutively active form of HIF\u20101\u03b1 (AdCA5). We assayed for coronary anomalies using anti\u2010alpha\u2010smooth muscle actin immunohistology. When incubated under abnormal oxygen levels or injected with a low titer of the AdCA5, coronary arteries displayed deviations from their normal proximal connections to the aorta. These deviations were similar to known clinical anomalies of coronary arteries. These findings indicated that developing coronary vessels may be subject to a level of regulation that is dependent on differential oxygen levels within cardiac tissues and subsequent HIF\u20101 regulation of gene expression. Developmental Dynamics 238:2688\u20132700, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.22089","type":"journal-article","created":{"date-parts":[[2009,9,23]],"date-time":"2009-09-23T17:47:10Z","timestamp":1253728030000},"page":"2688-2700","source":"Crossref","is-referenced-by-count":34,"title":["Altered hypoxia\u2010inducible factor\u20101 alpha expression levels correlate with coronary vessel anomalies"],"prefix":"10.1002","volume":"238","author":[{"given":"Jamie","family":"Wikenheiser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie 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