title: Iron chelation suppresses ferritin upregulation and attenuates vascular dysfunction in the aorta of angiotensin II-infused rats.
abstract: OBJECTIVE
  We have investigated whether long-term administration of angiotensin (Ang) II causes ferritin induction and iron accumulation in the rat aorta, and their possible relation to regulatory effects on gene expression and vascular function in Ang II-infused animals.
  
  
  RESULTS
  Sprague-Dawley rats were given Ang II for 7 days via subcutaneously implanted osmotic minipumps. Ang II infusion caused a >20-fold increase in ferritin protein expression over control values. Immunohistochemistry showed that Ang II infusion markedly increased the ferritin expression in the aortic endothelial and adventitial cells, with some of the latter being identified as monocytes/macrophages. Prussian blue staining showed that stainable iron was observed in the adventitial layer of aorta from Ang II-infused animals, but not in the endothelial layer. Chelation of iron suppressed aortic induction of ferritin and also the oxidative stress markers, heme oxygenase-1 and 4-hydroxynonenal-modified protein adducts. In addition, iron chelation attenuated Ang II-induced impairment of aortic relaxations in response to acetylcholine and sodium nitroprusside and suppressed upregulation of mRNA levels of monocyte chemoattractant protein-1. Iron chelation also partially attenuated the medial thickening and perivascular fibrosis induced by Ang II infusion for 4 weeks.
  
  
  CONCLUSIONS
  Ang II infusion caused ferritin induction and iron deposition in the aortas. These phenomena might have a role in the regulation of gene expression, impairment of vascular function, and arterial remodeling induced by Ang II, which are presumably mediated in part by enhancement of oxidative stress.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Hongo 7-3-1, Tokyo 113-8655, Japan. nobuishizka-tky@umin.ac.jp
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Ishizaka
authors.forename: Kan
authors.initials: K
authors.lastname: Saito
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Gen
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Ohno
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001052:Apoferritins; D018932:Chemokine CCL2 / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000150:complications*; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology*; D019190:Iron Overload / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007505:Iron-Dextran Complex / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000447:Aldehydes; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007502:Iron Chelating Agents; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007505:Iron-Dextran Complex; D005293:Ferritins; D001052:Apoferritins; D007501:Iron; D051547:Heme Oxygenase-1; D003676:Deferoxamine; C027576:4-hydroxy-2-nonenal; D009638:Norepinephrine