In Vitro Modeling of Bradykinin-Mediated Angioedema States

Kinins (peptides related to bradykinin, BK) are formed from circulating substrates, the kininogens, by the action of two proteases, the kallikreins. The only clinical application of a BK receptor ligand, the B2 receptor antagonist icatibant, is the treatment of the rare hereditary angioedema (HAE) c...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2020-08, Vol.13 (9), p.201
Main Authors: Marceau, François, Bachelard, Hélène, Charest-Morin, Xavier, Hébert, Jacques, Rivard, Georges E.
Format: Article
Language:English
Subjects:
acquired angioedema
analytical techniques for kinins
Angioedema
Antibodies
bradykinin
Edema
Endothelium
Enzymes
hereditary angioedema
Immunoassay
kallikrein–kinin system
Mutation
Peptides
Permeability
Plasma
Review
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Summary:Kinins (peptides related to bradykinin, BK) are formed from circulating substrates, the kininogens, by the action of two proteases, the kallikreins. The only clinical application of a BK receptor ligand, the B2 receptor antagonist icatibant, is the treatment of the rare hereditary angioedema (HAE) caused by the deficiency of C1-esterase inhibitor (C1-INH). Less common forms of HAE (genetic variants of factor XII, plasminogen, kininogen) are presumably mediated by increased BK formation. Acquired forms of BK-mediated angioedema, such as that associated with angiotensin-I converting enzyme (ACE) inhibition, are also known. Antibody-based analytical techniques are briefly reviewed, and support that kinins are extremely short-lived, prominently cleared by ACE. Despite evidence of continuous activation of the kallikrein–kinin system in HAE, patients are not symptomatic most of the time and their blood or plasma obtained during remission does not generate excessive immunoreactive BK (iBK), suggesting effective homeostatic mechanisms. HAE-C1-INH and HAE-FXII plasmas are both hyperresponsive to fibrinolysis activation. On another hand, we suggested a role for the alternate tissue kallikrein–kinin system in patients with a plasminogen mutation. The role of the BK B1 receptor is still uncertain in angioedema states. iBK profiles under in vitro stimulation provide fresh insight into the physiopathology of angioedema.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph13090201