title: Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.
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.
  
  
  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.
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sawada
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hao
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. ynaito@hyo-med.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Oboshi
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirotani
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Mitsuno
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.affiliation: From the Cardiovascular Division, Department of Internal Medicine (H.S., Y.N., M.O., S. Hirotani, T.M.), Department of Surgical Pathology (H.H., S. Hirota), and Department of Cardiovascular Surgery (M.M., Y.M.), Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001011:Aorta / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019190:Iron Overload / Q000503:physiopathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018345:Mice, Knockout; D018384:Oxidative Stress; D010766:Phosphorylation; D011990:Receptors, Transferrin / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003849:Deoxyguanosine; D048031:JNK Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; D011990:Receptors, Transferrin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C480029:Tfrc protein, mouse
keywords: aneurysm; inflammation; iron; oxidative stress