教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm. |
掲載誌名 | 正式名:Arteriosclerosis, thrombosis, and vascular biology 略 称:Arterioscler Thromb Vasc Biol ISSNコード:1524-4636(Electronic)1079-5642(Linking) |
巻・号・頁 | 35(6),pp.1507-14 |
著者・共著者 | Sawada Hisashi, Hao Hiroyuki, Naito Yoshiro, Oboshi Makiko, Hirotani Shinichi, Mitsuno Masataka, Miyamoto Yuji, Hirota Seiichi, Masuyama Tohru |
発行年月 | 2015/06 |
概要 | OBJECTIVE:Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models.APPROACH AND RESULTS:Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area inAPPROACH AND RESULTS:human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive.CONCLUSIONS:Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression. |
DOI | 10.1161/ATVBAHA.115.305586 |
PMID | 25882069 |