Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro

M. B. Juckett, J. Balla, G. Balla, J. Jessurun, H. S. Jacob, G. M. Vercellotti

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Abstract

Low density lipoprotein (LDL), if it becomes oxidized, develops several unique properties including the capacity to provoke endothelial cytotoxicity via metal-catalyzed free radical-mediated mechanisms. As we previously have shown that iron-catalyzed oxidant injury to endothelial cells can be attenuated by the addition of exogenous iron chelators such as the lazaroids and deferoxamine, we have examined whether the endogenous iron chelator, ferritin, might provide protection from oxidized LDL. LDL oxidized by iron- containing hemin and H2O2 is toxic to endothelial cells in a time- and dose-dependent fashion. Endothelial cell ferritin content is increased by pretreatment of cells with iron compounds or by the direct addition of exogenous apoferritin; ferritin-loaded cells are markedly resistant to the toxicity caused by oxidized LDL. Iron inactivation by ferritin depends on its ferroxidase activity. When a recombinant human ferritin heavy chain mutant, 222, which is devoid of ferroxidase activity, is added to endothelial cells, unlike the excellent protection afforded by the wild-type recombinant heavychain, endothelial cells are not protected from oxidized LDL. To assess the in vivo relevance of our observation, we examineed human coronary arteries of cardiac explants taken from patients with end-stage atherosclerosis. Large amounts of immunoreactive ferritin are focally detected in atherosclerotic lesions, specifically in the myofibroblasts, macrophages, and endothelium without a notable increase in Prussian blue- detectable iron. These findings suggest that ferritin may modulate vascular cell injury in vivo.

Original languageEnglish
Pages (from-to)782-789
Number of pages8
JournalAmerican Journal of Pathology
Volume147
Issue number3
Publication statusPublished - Jan 1 1995

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Juckett, M. B., Balla, J., Balla, G., Jessurun, J., Jacob, H. S., & Vercellotti, G. M. (1995). Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro. American Journal of Pathology, 147(3), 782-789.