TNF induces distinct gene expression programs in microvascular and macrovascular human endothelial cells

The relevance of the diversity of endothelial cells (ECs) for the response to inflammatory stimuli is currently not well defined. Using oligonucleotide microarray technique, we systematically analyzed the tumor necrosis factor (TNF)-induced expression profile in human microvascular ECs (HMEC) and macrovascular human umbilical vein ECs (HUVEC), analyzing 13,000 human genes by microarray analysis. Using strict inclusion and exclusion criteria, microarray analysis revealed that about half of the TNF-induced genes were specific for HMEC-1 or HUVEC. The microarray data could widely be confirmed by quantitative reverse transcriptase-polymerase chain reaction and at the protein level. It is interesting that the majority of those genes regulated depending on the cell type encoded for chemokines, cytokines, and cell surface molecules. Our results argue for a more careful consideration of specific effects restricted to distinct subtypes of ECs. The establishment of EC type-specific expression patterns may thus provide the basis for a selective manipulation of specific endothelial subtypes in different inflammatory diseases.