Published online before print August 11, 2005, doi: 10.1161/01.ATV.0000181763.57495.2b
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© 2005 American Heart Association, Inc.
Vascular Biology |
Iron Chelation Suppresses Ferritin Upregulation and Attenuates Vascular Dysfunction in the Aorta of Angiotensin II–Infused Rats
From the Department of Cardiovascular Medicine (N.I., K.S., G.M., M.O., R.N.), University of Tokyo Graduate School of Medicine, and the Department of Pathology, Wakayama Medical College (I.M.), Japan.
Correspondence to Dr Nobukazu Ishizaka, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail nobuishizka-tky{at}umin.ac.jp
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.
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. 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.
Key Words: ferritin • heme oxygenase • hypertension • oxidative stress • vascular relaxation
Related Article:
Arterioscler. Thromb. Vasc. Biol. 2005 25: 2235-2237.
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  D. E. Ferrara and W. R. Taylor Iron Chelation and Vascular Function: In Search of the Mechanisms Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2235 - 2237. [Full Text] [PDF]
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