Research summary 2007

The mechanisms that regulate the generation of new vessels and endothelial cell differentiation/activation are potential drug targets in several fields of medicine, because such targeting may enable control of cancer growth and metastasis, enhance the healing of ischemic lesions and modulate the leukocyte migration of inflammatory disorders including allograft rejection.

VEC has focused on understanding the role of interleukin-33 in endothelial cell activation, revealing that it is most likely involved in the transition from one vascular phenotype to another. Moreover, studies designed at understanding how chemokines are targeted to compartments of regulated secretion and the role of such secretion in vivo is ongoing.

Specifically, we have generated chimeras of interleukin-8 and IP-10 and shown that loop 2 of the tertiary structure contains aminoacids required for proper storage of IL-8 in Weibel-Palade bodies. A third line of experiments is focused at understanding the molecular in vivo actions of the angiogenesis inhibitor endostatin.

In collaboration with Diagnostic section 2, we have generated the first transcriptional profile of endothelial cells during experimental allograft rejection and identified more than 100 differentially expressed transcripts whose further verification and differentiation is ongoing.