The role of Factor-VII activating protease in the generation of bradykinin in patients with hereditary angioedema

Patients with hereditary angioedema (also known as Quincke edema) are known to
have a protein deficiency called C1-esterase inhibitor in their blood. During
angioedema which can be caused for example by stress, fever or infection, there
is a shortage of this inhibitor and an excess of another protein called
bradykinin. This results in a high concentration of bradykinin in the
bloodstream. Bradykinin is an important factor in the permeability in the blood
vessels. The high concentration of the bradykinin in the blood causes high
permeability of water within the blood vessels which results in oedema. Through
scientific experiments it has recently been discovered that a protein factor
VII activating protease (FSAP) may cause the production of bradykinin within
the body. Normally the FSAP is inactive. When there is trauma or inflammation
in the body the blood cells die off and FSAP can be activated and produce
bradykinin.

1) Does FSAP activation in plasma of HAE patients contributes to bradykinin
formation? 2) Study the inhibitory efficacy of c1-inhibitor towards kallikrein
and FSAP towards bradykinin formation in a endothelial cell-based system. 3)
test the efficacy of plasma inhibitors other than c1-inhibitor toward activated
FSAP and kallikrein with regard to bradykinin formation in a endothelial
cell-based system . These experiments will be performed with plasma of HAE
patients (n=40) and of healthy controls (n=40)

At patients with HAE the concentration of FSAP and bradykinine will be measured
in blood. Also we will investigated whether genetic material in patients with
HAE have a tendency to produce active forms of FSAP compared to healthy people.

one blood sampling (40 ml) through venapunctures and questionnaire. Risks are
not to be expected.