Gene expression profiles of microvascular endothelial cells after stimuli implicated in the pathogenesis of vasoocclusion.

Altered gene expression in endothelial cells interacting with sickle red blood cells (RBC) and other blood components, in particular the pro-inflammatory cytokines, is an essential step in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD). Using cDNA arrays, we monitored gene expression profiles of human lung microvascular endothelial cells (HMVEC-L) after stimuli that are likely involved in the pathogenesis of vasoocclusion. We detected increased expression of multiple genes in HMVEC-L after their exposure to pro-inflammatory cytokines TNFalpha and IL-1beta and to RBC with increased external exposure of phosphatidylserine and RBC from a patient with SC hemoglobin. While some of these genes have previously been implicated in vascular damage, many represent new targets for investigation of the pathogenesis of vasoocclusion in SCD.