title: C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress.
abstract: C1 inhibitor (C1-INH, also known as SERPING1) can be deficient in plasma as a result of genetic or acquired conditions, and this causes an episodic, local increase in vascular permeability in the subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Bradykinin, the mediator of the increase in vascular permeability, is released on inappropriate activation of the contact system, which is controlled by C1 inhibitor. Therapy aims to reverse or prevent angioedema. Advances in understanding the complex effects of C1-INH deficiency at the molecular level have led to new molecular-targeted approaches. Three new treatments, an inhibitor of kallikrein to prevent bradykinin release, an antagonist of the bradykinin receptor to prevent its action and a recombinant human C1-INH produced in transgenic animals, are under clinical evaluation currently. Here, we review the molecular mechanisms underlying angioedema due to C1-inhibitor deficiency and clinical progress using molecular-targeted interventions.
authors.affiliation: Department of Internal Medicine, University of Milan, Mangiagalli e Regina Elena, Milan 20122, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanichelli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Foieni
authors.forename: Sonia
authors.initials: S
authors.lastname: Caccia
authors.forename: Marco
authors.initials: M
authors.lastname: Cicardi
mesh_terms: D000799:Angioedema / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D001920:Bradykinin / Q000378:metabolism; D002199:Capillary Permeability; D050718:Complement C1 Inhibitor Protein / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D050718:Complement C1 Inhibitor Protein; D010447:Peptide Hydrolases; D007610:Kallikreins; D001920:Bradykinin