Aortic Iron Overload with Oxidative Stress and Inflammation in Human and Murine Abdominal Aortic Aneurysm

Hisashi Sawada, Hiroyuki Hao, Yoshiro Naito, Makiko Oboshi, Shinichi Hirotani, Masataka Mitsuno, Yuji Miyamoto, Seiichi Hirota, Tohru Masuyama

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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 in 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.

Original languageEnglish
Pages (from-to)1507-1514
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume35
Issue number6
DOIs
StatePublished - Jun 27 2015

Keywords

  • aneurysm
  • inflammation
  • iron
  • oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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