Hypoxia regulates inflammatory gene expression in endothelial cells

Abstract

Hypoxia can activate the endothelium toward a pro-inflammatory phenotype and enhance leukocyte adhesion. This process is involved in pathological conditions such as vascular remodeling or ischemia–reperfusion injury. This study was aimed to obtain a global picture of the response of the endothelial cells to hypoxia with respect to inflammatory genes. To this purpose, we used a low density DNA microarray specifically designed to quantitate the expression of genes involved in the inflammatory pathways and a customized real-time PCR array. The expression of several pro-inflammatory genes known to be NF-kB target genes was decreased after the incubation of endothelial cells under hypoxia. In parallel, a decrease in the DNA binding activity of this transcription factor was observed. On the other hand, HIF-1 DNA binding activity was increased as well as the expression of several genes known to be regulated by this factor. Among them are several pro-inflammatory genes whose overexpression could account for the increase in leukocyte adhesion to the hypoxic endothelial cells. We concluded that hypoxia does not shift the endothelial cell phenotype to a more pro-inflammatory one probably because of a decrease in the expression of several cytokines. On the other hand, a clear response to hypoxia was observed with HIF-1 probably playing an important role in this process.