Expression of heme oxygenase-1 by endothelial cells: A protective response to injury in transplantation

Endothelial cells (EC) play a pivotal role in the regulation of inflammation by expressing a series of pro- and anti-inflammatory genes that are associated with the activation of these cells. The nature of these genes and the regulation of their expression may be particularly important for the outcome of immediately vascularised transplants. We refer to the set of anti-inflammatory genes that are expressed during EC activation as protective genes because they can block the expression of pro-inflammatory genes associated with EC activation and prevent EC apoptosis. In this review we discuss data that supports the hypothesis that expression of these protective genes in a transplanted organ can promote its survival. We will focus on the description of one such protective gene, heme oxygenase-1 (HO-1). The first part of the review discusses the potential role of EC activation in regulating inflammatory responses such as those associated with the rejection of transplanted organs. The second part discusses the molecular mechanisms that regulate the expression of HO-1 in EC as well as the molecular mechanism by which the expression of this gene can regulate EC activation. The third part discusses potential mechanisms by which HO-1 may contribute to suppress different phases of the rejection of transplanted organs, e.g., ischaemia reperfusion injury, acute rejection and chronic failure. In the last part we discuss the role of HO-1 in establishing long-term survival of organs that are transplanted across different species, an approach referred to as xenotransplantation.