Abstract
There has been increasing evidence suggesting the potent anti‐inflammatory roles of heme oxygenase‐1 (HO‐1) in protecting renal tubular epithelial cells, vascular endothelial cells, and circulating monocytes. Based on these findings, novel therapeutic interventions have been proposed to control the expression of endothelial HO‐1 levels to ameliorate various vascular diseases. We evaluated the effect of HO‐1 gene transfer into an anchorage‐dependent cell, ECV304. Effect of HO‐1 production on the cell injury induced by hydrogen peroxide was evaluated after hemin stimulation and after HO‐1 gene transfection. Morphological changes and the induction of various anti‐apoptotic proteins were examined at the same time. Levels of HO‐1 expression were variable in different clones of HO‐1‐transfected ECV304 cells. Among these, the clones with moderate levels of HO‐1 expression were significantly more resistant to oxidative stress. In contrast, those with the highest levels of HO‐1 exhibited paradoxically enhanced susceptibility to oxidative injury. Interestingly, the cell survival after oxidative stress was in parallel with the levels of Bcl‐2 expression and of fibronectin receptor, α5 integrin. It is suggested from these results, that excessive HO‐1 not only leads to enhanced cell injury, but also prolongs the repair process of the injured endothelial tissue. However, HO‐1 reduces the oxidative cell injury and protects the endothelial cells, if its expression is appropriately controlled. © 2004 Wiley‐Liss, Inc.