Heme, heme oxygenase, and ferritin: How the vascular endothelium survives (and dies) in an iron-rich environment

József Balla, Gregory M. Vercellotti, Viktória Jeney, Akihiro Yachie, Zsuzsa Varga, Harry S. Jacob, John W. Eaton, György Balla

Research output: Contribution to journalReview articlepeer-review

129 Scopus citations

Abstract

Iron-derived reactive oxygen species are involved in the pathogenesis of numerous vascular disorders. One abundant source of redox active iron is heme, which is inherently dangerous when it escapes from its physiologic sites. Here, we present a review of the nature of heme-mediated cytotoxicity and of the strategies by which endothelium manages to protect itself from this clear and present danger. Of all sites in the body, the endothelium may be at greatest risk of exposure to heme. Heme greatly potentiates endothelial cell killing mediated by leukocytes and other sources of reactive oxygen. Heme also promotes the conversion of low-density lipoprotein to cytotoxic oxidized products. Hemoglobin in plasma, when oxidized, transfers heme to endothelium and lipoprotein, thereby enhancing susceptibility to oxidant-mediated injury. As a defense against such stress, endothelial cells upregulate heme oxygenase-1 and ferritin. Heme oxygenase opens the porphyrin ring, producing biliverdin, carbon monoxide, and a most dangerous product - redox active iron. The latter can be effectively controlled by ferritin via sequestration and ferroxidase activity. These homeostatic adjustments have been shown to be effective in the protection of endothelium against the damaging effects of heme and oxidants; lack of adaptation in an iron-rich environment led to extensive endothelial damage in humans.

Original languageEnglish (US)
Pages (from-to)2119-2137
Number of pages19
JournalAntioxidants and Redox Signaling
Volume9
Issue number12
DOIs
StatePublished - Oct 1 2007

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