Heme Oxygenase-1-Mediated Protection: Potential Role of Nonheme Iron–Nitric Oxide Complexes

To the Editor: In a recent paper, Tulis and coworkers1 reported that transfectional overexpression of heme oxygenase-1 (HO-1) inhibits arterial remodeling after balloon angioplasty via a mechanism involving apoptosis. HO-1 is a stress response protein that degrades heme to carbon monoxide, biliverdin, and nonheme iron. In general, overexpression of HO-1 plays a cytoprotective role against a variety of oxidative stimuli. Interestingly, cells overexpressing HO-1 exhibit low levels of free iron because of the upregulation of ferritin and the extraction of iron into the extracellular space.2 The elimination of pro-oxidant iron from the cell is considered to be an important mechanism of HO-1–mediated protection against oxidative stress.2 How HO-1 overexpression stimulates apoptosis in the medial wall of injured artery is unclear. We believe that, among potential mechanisms of …