Regolazione dei geni coinvolti nella patogenesi dell’angioedema ereditario da carenza di C1 inibitore

Hereditary Angioedema (HAE) is a disabeling and potentially lethal disease due to genetic deficiency of C1 inhibitor. The aim of the project was to provide a better understanding on the pathogenesis of symptoms to improve the therapeutic approaches. Using microarray approach, we identified two new genes that are activated during symptoms. These two genes may directly affect the increase in vascular permeability that characterizes the formation of angioedema. Based on these results we are now studying the possibility to have these genes as new targets for therapy. Biochemical studies on patients with different disease state allowed to identify one of the proteins involved in angioedema formation (high molecular weight kininogen) as a marker which correlates with dsease severity. This marker can now be used for monitoring patients during treatment. We expanded the knowledge on the molecular mechanisms underlaying C1 inhibitor deficiency. These results are preliminary to the development of molecular strategies to modify the production of C1 inhibitor and to correct the genetic defect.