Endothelial cell function in patients with hereditary angioedema: elevated soluble E-selectin level during inter-attack periods.
BACKGROUND
The bradykinin pathway in the pathomechanism of hereditary angioedema due to C1-inhibitor deficiency (henceforward "hereditary angioedema") has been thoroughly studied; however, much less is known about endothelial cell function. Enhanced endothelial cell permeability is obvious during edematous attacks, but not during inter-attack periods. Our knowledge about other endothelial characteristics is even more incomplete.


OBJECTIVE
Therefore the aim of this study was to characterize endothelial cell function in hereditary angioedema patients during symptom-free, inter-attack periods.


METHODS
We measured the serum levels of soluble E-selectin, endothelin-1, and von Willebrand factor along with collagen-binding activity in 49 hereditary angioedema patients and in 50 healthy controls.


RESULTS
Endothelin-1 and von Willebrand factor level, as well as its collagen-binding activity, were similar in hereditary angioedema patients and in controls; however, we found elevated soluble E-selectin levels in the patients. Interestingly, soluble E-selectin concentration did not correlate with any of the inflammatory markers or smoking, and it is not the consequence of the known E-selectin/C1-inhibitor interaction (an analytical phenomenon). In a multiple logistic regression model, the difference in soluble E-selectin between hereditary angioedema patients and controls remained highly significant when adjusted for age, gender, smoking, C-reactive protein, and AB0 blood groups.


CONCLUSIONS
These results demonstrate that in hereditary angioedema, the majority of endothelial functions are normal during inter-attack periods; however, soluble E-selectin levels are elevated. The higher soluble E-selectin plasma concentration is unlikely to result from inflammation; rather, it reflects enhanced shedding mechanisms.
Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. czucz@kut.sote.hu
Judit
J
Czúcz
Gyula
G
Schaffer
Dorottya
D
Csuka
Szilvia
S
Walentin
Jan
J
Kunde
Zoltán
Z
Prohászka
Henriette
H
Farkas
László
L
Cervenak
D000328:Adult; D054179:Angioedemas, Hereditary / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism; D019040:E-Selectin / Q000097:blood / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D050718:Complement C1 Inhibitor Protein; D019040:E-Selectin