Research in WRI

VEGF is induced in tissue hypoxia, for example in embryos and in tumors. VEGF-C and VEGF-D can directly induce lymphangiogenesis by activating VEGFR-3 in lymphatic endothelial cells. It binds VEGFR-1 and VEGFR-2 in nearby endothelial cells initiating the process of new vessel growth. Although antibodies that block VEGF have been successfully used in tumor therapy, attempts to use VEGF for proangiogenic therapy in tissue ischemia have been hampered by its property to increase vascular permeability and promote angioma-like formation.

VEGF-B has remained rather enigmatic since its identification more than 15 years ago. VEGF-B expression levels are highest in tissues that need high levels of energy metabolism. Mice deficient in VEGF-B are viable and fertile and display only a mild phenotype in some mouse strains. Supraphysiological VEGF-B levels obtained by adenoviral transfection induce capillary enlargement in the heart, but the ability of VEGF-B to promote angiogenesis directly is at best very weak. However, based on new findings on VEGF-B by the Alitalo group, a breakthrough in the therapy of cardiovascular ischemia has become closer. VEGF-B may also play an important role in the development of type 2 diabetes and metabolic disease.

In addition to the VEGFs, the angiopoeitin growth factors (ANG, also termed ANGPT) and their endothelial TIE receptors are significant regulators of both lymphatic and blood vessels. Recently, much interest has focused on the function of the ANG-TIE system in a number of diseases, including sepsis, acute respiratory distress syndrome, diabetes and cancer, among others, and on the possibilities to target the ANG-TIE system in the various diseases.