Literature DB >> 12356639

Iron overload augments angiotensin II-induced cardiac fibrosis and promotes neointima formation.

Nobukazu Ishizaka1, Kan Saito, Haruo Mitani, Ieharu Yamazaki, Masataka Sata, Shin-ichi Usui, Ichiro Mori, Minoru Ohno, Ryozo Nagai.   

Abstract

BACKGROUND: Abnormal iron deposition may cause oxidant-induced damage in various organs. We have previously reported that continuous administration of angiotensin II to rats results in an overt iron deposition in the renal tubular epithelial cells, which may have a role in angiotensin II-induced renal damage. In the present study, we investigated the role of iron in the development of cardiac injury induced by angiotensin II. METHODS AND
RESULTS: Angiotensin II was continuously infused to rats at a dose of 0.7 mg/kg per day for 7 consecutive days. No iron deposits were observed in the hearts of untreated rats, whereas iron deposition was seen in the cells in the subepicardial and granulation regions after angiotensin II infusion. Concomitant administration of deferoxamine, an iron chelator, significantly reduced the extent of cardiac fibrosis, which suggests that iron deposition aggravates the cardiac fibrosis induced by angiotensin II. Iron overload caused by the administration of iron-dextran resulted in an augmentation of cardiac fibrosis and the generation of neointimal cells in the coronary artery in angiotensin II-infused rats. By contrast, neointima was not formed in the cardiac vessels in norepinephrine-infused rats with iron overload.
CONCLUSIONS: Cardiac iron deposition may be involved in the development of cardiac fibrosis induced by angiotensin II. In addition, iron overload may enhance the formation of neointima under conditions of increased circulating angiotensin II but not catecholamines.

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Year:  2002        PMID: 12356639     DOI: 10.1161/01.cir.0000031161.77536.02

Source DB:  PubMed          Journal:  Circulation        ISSN: 0009-7322            Impact factor:   29.690


  13 in total

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