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Cited by 55Renin-Angiotensin System StudiesNitric Oxide and Endothelin EffectsIron Metabolism and Disorders

Iron Chelation Suppresses Ferritin Upregulation and Attenuates Vascular Dysfunction in the Aorta of Angiotensin II–Infused Rats

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Ishizaka, Nobukazu, Saito, Kan, Mori, Ichiro, Matsuzaki, Gen, Ohno, Minoru, Nagai, Ryozo·2005·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/01.atv.0000181763.57495.2b
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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. Methods and 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. Conclusion— 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.

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Authors
Ishizaka, N., Saito, K., Mori, I., Matsuzaki, G., Ohno, M., & Nagai, R.
Affiliations
Wakayama Medical University (JP)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2005-11
Volume
25
Issue
11
Pages
2282-2288
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/01.atv.0000181763.57495.2b
OpenAlex
W2119756492
Cited by
55
References
40
Citations by year
2026: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 2
FWCI
2.74
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Novartis Foundation
  • Japan Society for the Promotion of Science (13671098)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
angiotensin II, ferritin, iron chelation, aorta, vascular dysfunction, oxidative stress, heme oxygenase-1, 4-hydroxynonenal, MCP-1, perivascular fibrosis, arterial remodeling, endothelial cells, iron accumulation
MeSH terms
Aldehydes, Angiotensin II, Animals, Aorta, Aortic Diseases, Apoferritins, Deferoxamine, Ferritins, Hypertension, Iron, Iron Chelating Agents, Iron-Dextran Complex, Male, Norepinephrine, Receptors, Transferrin, RNA, Messenger, Vasoconstrictor Agents, Vasodilation, Up-Regulation, Rats, Sprague-Dawley, Oxidative Stress, Chemokine CCL2, Iron Overload, Rats, Heme Oxygenase-1

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