Purpose: Angioedema (AE) due to inherited or acquired
deficiencies of C1 inhibitor (C1-INH) is characterized by localized
swelling of deeper layers of the skin or submucosal tissues,
becoming particularly life threatening if it occurs in the upper
respiratory tract. C1-INH regulates the release of bradykinin
which can enhance permeability of post-capillary venules
interacting with its receptors. The drugs currently used are
more symptomatic than curative, so we sought to identify the
molecular mechanisms responsible for the induction of vascular
permeability.
Methods: We used a transwell in vitro model with a filter covered
by primary human endothelial cells (EC), in the upper chamber
we add the fluorescent-BSA and the stimuli and the BSA leaked
into the lower chamber was evaluated using a Fluorescence
reader.
Results: EC were incubated with plasma collected from patients
during attack (APL) and the presence of C1-INH in the majority
of the patients was able to block the permeability. To mimic the
in vivo situation we stimulated the EC with the APL for 30 min
and then the SN was collected and used to stimulate the ECs in
the transwell model. In that case the inhibition of the leakage
by C1-INH was not seen in all the patients. This observation was
further confirmed by using the plasma collected from 1 patient
before and 1 h after the clinical treatment with C1-INH, indeed
there is no difference in the EC leakage induced by the plasma
before and after the treatment.
Discussions: The inhibition of endothelial leakage induced by
APL stimulation by C1-INH indicates the involvement of that
molecule in controlling the onset of AE attacks, although the
inability of C1-INH to completely block the permeabilizing effect
of the SN indicates that after the activation of the cells there are
other molecules involved.
Conclusion: Since the clinical treatment of AE can be done with
different drugs besides C1-INH we have to analyze the most
appropriate therapeutic approach.
