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Significant HIF-1\u03b1 expression could be found at the rupture edge at human abdominal aortic aneurysm (AAA) tissues. While our initial <jats:italic>in vitro<\/jats:italic> experiments had shown that deferoxamine (DFO) could attenuate angiotensin II (AngII) induced endothelial activations; we unexpectedly found that DFO augmented the severity of AngII-induced AAA, at least partly through increased accumulation of HIF-1\u03b1. The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1\u03b1 and promote AAA development. AngII induced AAA in hyperlipidemic mice model was used. DFO, as a prolyl hydroxylase inhibitor, stabilized HIF-1\u03b1 and augmented MMPs activities. Aneurysmal-prone factors induced HIF-1\u03b1 can cause overexpression of MMP-2 and MMP-9 and promote aneurysmal progression. Pharmacological HIF-1\u03b1 inhibitors, digoxin and 2-ME could ameliorate AngII induced AAA <jats:italic>in vivo<\/jats:italic>. HIF-1\u03b1 is pivotal for the development of AAA. Our study provides a rationale for using HIF-1\u03b1 inhibitors as an adjunctive medical therapy in addition to current cardiovascular risk-reducing regimens.<\/jats:p>","DOI":"10.1038\/srep28612","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T10:21:08Z","timestamp":1467368468000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Inhibition of hypoxia inducible factor-1\u03b1 attenuates abdominal aortic aneurysm progression through the down-regulation of matrix metalloproteinases"],"prefix":"10.1038","volume":"6","author":[{"given":"Shih-Hung","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Hsun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Juei","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jen","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hsing","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen-Chun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaw-Wen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shing-Jong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,1]]},"reference":[{"key":"BFsrep28612_CR1","doi-asserted-by":"publisher","first-page":"e463","DOI":"10.1161\/circulationaha.106.174526","volume":"113","author":"AT Hirsch","year":"2006","unstructured":"Hirsch, A. 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