Heme, heme oxygenase and ferritin in vascular endothelial cell injury

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

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Iron-derived reactive oxygen species are implicated in the pathogenesis of numerous vascular disorders including atherosclerosis, microangiopathic hemolytic anemia, vasculitis, and reperfusion injury. One abundant source of redox active iron is heme, which is inherently dangerous when released from intracellular heme proteins. The present review concerns the involvement of heme in vascular endothelial cell damage and the strategies used by endothelium to minimize such damage. Exposure of endothelium to heme greatly potentiates cell killing mediated by polymorphonuclear leukocytes and other sources of reactive oxygen. Free heme also promotes the conversion of low-density lipoprotein (LDL) into cytotoxic oxidized products. Only because of its abundance, hemoglobin probably represents the most important potential source of heme within the vascular endothelium; hemoglobin in plasma, when oxidized, transfers heme to endothelium and LDL, thereby enhancing cellular susceptibility to oxidant-mediated injury. As a defense against such toxicity, upon exposure to heme or hemoglobin, endothelial cells up-regulate heme oxygenase-1 and ferritin. Heme oxygenase-1 is a heme-degrading enzyme that opens the porphyrin ring, producing biliverdin, carbon monoxide, and the most dangerous product - free redox active iron. The latter can be effectively controlled by ferritin via sequestration and ferroxidase activity. Ferritin serves as a protective gene by virtue of antioxidant, antiapoptotic, and antiproliferative actions. These homeostatic adjustments have been shown effective in the protection of endothelium against the damaging effects of exogenous heme and oxidants. The central importance of this protective system was recently highlighted by a child diagnosed with heme oxygenase-1 deficiency, who exhibited extensive endothelial damage.

Original languageEnglish (US)
Pages (from-to)1030-1043
Number of pages14
JournalMolecular Nutrition and Food Research
Issue number11
StatePublished - Nov 1 2005


  • Atherosclerosis
  • Endothelial cell injury
  • Ferritin
  • Heme
  • Heme oxygenase


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