@mastersthesis {72,
	title = {VEGFR-3 Ligands and Lymphangiogenesis},
	volume = {PhD Thesis},
	year = {2002},
	abstract = {Most of us have seen their own blood at one or the other time. The occasion might have been
a small accident or in unfortunate cases a severe blood loss caused by a major injury. We also
can feel our heart beating and the resulting pressure wave, the pulse. The existence of the car-
diovascular system is obvious to us. Unlike the cardiovascular system, the lymphatic system
has, until recently, escaped notable attention not only by the laymen, but also by the scientific
community. It is unclear why the lymphatic system originally developed in higher vertebrates.
Now, its main function seems to be to collect fluid that has leaked from the blood vessels and
to return it into the cardiovascular system. Much of our knowledge about the development and
structure of the lymphatic system is of considerable age, and it has been said that there has not
been any progress in our understanding since the fine structure of the lymphatics was described
with the introduction of the electron microscope.
Vascular endothelial growth factor (VEGF) is the principal direct inducer of blood vessel
growth, but it does not promote the growth of lymphatic vessels. This study demonstrates for
the first time specific lymphangiogenesis as a response to the VEGF homologue VEGF-C.
Overexpression of full length VEGF-C under the keratin-14 promoter in the skin of transgenic
mice caused a proliferation of the lymphatic endothelium and lymphatic vessel enlargement. In
the chorioallantoic membrane assay, the mature form of VEGF-C was also largely specific for
lymphatic endothelial cells. A newly discovered close homologue of VEGF-C, VEGF-D was
then shown to have the same receptor-binding pattern as VEGF-C.
Contrary to the interaction of VEGF with its receptors, VEGF-C interaction with VEGFR-3 has
not been analyzed at the molecular level. The structural determinants of VEGFR-3 binding were
characterized in relation to VEGF using a non-random family shuffling approach with VEGF
and VEGF-C as parent molecules. This approach led to the identification of VEGF/VEGF-C
mosaic molecules that showed novel receptor binding profiles and a panel of these molecules
was used to delineate the requirements of specific receptors in the induction of angiogenesis
versus lymphangiogenesis.},
	url = {http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/jeltsch},
	author = {Jeltsch, Michael}
}
