Endothelial cell activation in inflammation: lessons from mutant mouse models

Dysregulation of the inflammatory response is a causative or contributing factor in many cardiovascular pathologies. Molecular mechanisms involved in these processes indicate that the vascular endothelium is an important facet in the regulation of inflammation. Gene targeted mutational studies in the mouse have shown that adhesion and signaling molecule expression within the endothelium participate in the pathogenic process of cardiovascular disease. These studies provide insight into genetic pathways that may be therapeutically relevant in both treatment and diagnostic regimens. However, we have also learned that the role of these pathways in endothelium during inflammatory diseases is complex, requiring further study to better understand specific mechanisms involved in endothelial cell dysfunction during cardiovascular disease. Alternative gene targeting techniques, such as the Cre-loxP system, are beginning to allow tissue specific investigation of genetic pathways within the endothelium; however, extensive use of this technology is limited. This review discusses the role of the endothelium during inflammation and the insights that have been gained from the use of gene targeted mutant mice.