title: Deficiency of plasminogen activator inhibitor 2 in plasma of patients with hereditary angioedema with normal C1 inhibitor levels.
abstract: Hereditary angioedema with normal C1 inhibitor levels (HAE-N) is associated with a Factor XII mutation in 30% of subjects; however, the role of this mutation in the pathogenesis of angioedema is unclear.
  
  
  
  We sought evidence of abnormalities in the pathways of bradykinin formation and bradykinin degradation in the plasma of patients with HAE-N both with and without the mutation.
  
  
  
  Bradykinin was added to plasma, and its rate of degradation was measured by using ELISA. Plasma autoactivation was assessed by using a chromogenic assay of kallikrein formation. Plasminogen activator inhibitors (PAIs) 1 and 2 were also measured by means of ELISA.
  
  
  
  PAI-1 levels varied from 0.1 to 4.5 ng/mL (mean, 2.4 ng/mL) in 23 control subjects, from 0.0 to 2 ng/mL (mean, 0.54 ng/mL) in patients with HAE-N with a Factor XII mutation (12 samples), and from 0.0 to 3.7 ng/mL (mean, 1.03 ng/mL) in patients with HAE-N without a Factor XII mutation (11 samples). PAI-2 levels varied from 25 to 87 ng/mL (mean, 53.8 ng/mL) in control subjects and were 0 to 25 ng/mL (mean, 4.3 ng/mL) in patients with HAE-N with or without the Factor XII mutation. Autoactivation at a 1:2 dilution was abnormally high in 8 of 17 patients with HAE-N (4 in each subcategory) and could be corrected by supplemental C1 inhibitor in 4 of them. Bradykinin degradation was markedly abnormal in 1 of 23 patients with HAE-N and normal in the remaining 22 patients.
  
  
  
  Bradykinin degradation was normal in all but 1 of 23 patients with HAE-N studied. By contrast, there was a marked abnormality in PAI-2 levels in patients with HAE-N that is not seen in patients with C1 inhibitor deficiency. PAI-1 levels varied considerably, but a statistically significant difference was not seen. A link between excessive fibrinolysis and bradykinin generation that is estrogen dependent is suggested.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC. Electronic address: josephk@musc.edu.
authors.forename: Kusumam
authors.initials: K
authors.lastname: Joseph
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC.
authors.forename: Baby G
authors.initials: BG
authors.lastname: Tholanikunnel
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC.
authors.forename: Bethany
authors.initials: B
authors.lastname: Wolf
authors.affiliation: Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Bork
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, SC.
authors.forename: Allen P
authors.initials: AP
authors.lastname: Kaplan
mesh_terms: D054179:Angioedemas, Hereditary / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D001920:Bradykinin / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D050718:Complement C1 Inhibitor Protein / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005174:Factor XII / Q000235:genetics; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood / Q000172:deficiency*; D059748:Proteolysis
chemical_list: D050718:Complement C1 Inhibitor Protein; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D005174:Factor XII; D007610:Kallikreins; D001920:Bradykinin
keywords: C1 inhibitor; Hereditary angioedema; bradykinin; plasminogen activator inhibitor