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Individuals with sickle cell disease who co\u2010inherit the loss of one or two \u03b1\u2010globin genes have been known to have reduced risk of morbid outcomes, but the underlying mechanism is unknown. While \u03b1\u2010globin gene deletions affect sickle red cell deformability, the \u03b1\u2010globin genes and protein are also present in the endothelial wall of human arterioles and participate in nitric oxide scavenging during vasoconstriction. Decreased production of \u03b1\u2010globin due to \u03b1\u2010thalassemia trait may thereby limit nitric oxide scavenging and promote vasodilation. To evaluate this potential mechanism, we performed flow\u2010mediated dilation and microvascular post\u2010occlusive reactive hyperemia in 27 human subjects (15 missing one or two \u03b1\u2010globin genes and 12 healthy controls). Flow\u2010mediated dilation was significantly higher in subjects with \u03b1\u2010trait after controlling for age (<jats:italic>P<\/jats:italic> =\u2009.0357), but microvascular perfusion was not different between groups. As none of the subjects had anemia or hemolysis, the improvement in vascular function could be attributed to the difference in \u03b1\u2010globin gene status. This may explain the beneficial effect of \u03b1\u2010globin gene loss in sickle cell disease and suggests that \u03b1\u2010globin gene status may play a role in other vascular diseases.<\/jats:p>","DOI":"10.1002\/ajh.26058","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T12:33:16Z","timestamp":1606566796000},"page":"277-281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Loss of alpha\u2010globin genes in human subjects is associated with improved nitric oxide\u2010mediated vascular perfusion"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-1775","authenticated-orcid":false,"given":"Christopher C.","family":"Denton","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics Children\u02bcs Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5211-6169","authenticated-orcid":false,"given":"Payal","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of General Pediatrics Children\u02bcs Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvie","family":"Suriany","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Pediatrics, Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Pediatrics, Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanwara","family":"Thuptimdang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Sunwoo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-7903","authenticated-orcid":false,"given":"Patjanaporn","family":"Chalacheva","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saranya","family":"Veluswamy","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Pediatrics Children\u02bcs Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Pulmonology Department of Pediatrics, Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-3439","authenticated-orcid":false,"given":"John C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Pediatrics, Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2086-9569","authenticated-orcid":false,"given":"Jon A.","family":"Detterich","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Pediatrics, Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C. 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