| Autor: |
Han, Eun D., MacFarlane, Ryan C., Mulligan, Aideen N., Scafidi, Jennifer, Davis, Alvin E. |
| Rok vydání: |
2002 |
| Předmět: |
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| Zdroj: |
Journal of Clinical Investigation. 109:1057-1063 |
| ISSN: |
0021-9738 |
| DOI: |
10.1172/jci200214211 |
| Popis: |
Heterozygosity for C1 inhibitor (C1INH) deficiency results in hereditary angioedema. Disruption of the C1INH gene by gene trapping enabled the generation of homozygous- and heterozygous-deficient mice. Mating of heterozygous-deficient mice resulted in the expected 1:2:1 ratio of wild-type, heterozygous, and homozygous-deficient offspring. C1INH-deficient mice showed no obvious phenotypic abnormality. However, following injection with Evans blue dye, both homozygous and heterozygous C1INH-deficient mice revealed increased vascular permeability in comparison with wild-type littermates. This increased vascular permeability was reversed by treatment with intravenous human C1INH, with a Kunitz domain plasma kallikrein inhibitor (DX88), and with a bradykinin type 2 receptor (Bk2R) antagonist (Hoe140). In addition, treatment of the C1INH-deficient mice with an angiotensin-converting enzyme inhibitor (captopril) increased the vascular permeability. Mice with deficiency of both C1INH and Bk2R demonstrated diminished vascular permeability in comparison with C1INH-deficient, Bk2R-sufficient mice. These data support the hypothesis that angioedema is mediated by bradykinin via Bk2R. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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