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Published on: September 28, 2015
The pathogenesis of hereditary angioedema
1Center for Blood Research, Harvard University Medical School, 800 Huntington Avenue, Boston, MA 02115-6303, USA. aldavis@cbr.med.harvard.edu
Summary
Hereditary angioedema (HAE) involves C1 inhibitor (C1INH) deficiency, leading to increased vascular permeability. Research suggests bradykinin mediates HAE, offering new therapeutic targets.
Area of Science:
- Immunology
- Biochemistry
- Genetics
Background:
- Hereditary angioedema (HAE) is characterized by episodic swelling due to C1 inhibitor (C1INH) deficiency.
- C1INH regulates contact system proteases like factor XIIa and plasma kallikrein, preventing excessive vascular permeability.
Purpose of the Study:
- To investigate the role of C1INH in regulating vascular permeability.
- To confirm the involvement of bradykinin in HAE pathogenesis.
- To establish a mouse model for testing HAE therapeutics.
Main Methods:
- Utilized C1INH-deficient mice to study vascular permeability.
- Administered C1INH, plasma kallikrein inhibitor (DX88), and bradykinin B2 receptor antagonist (Hoe140).
- Generated and analyzed mice deficient in both C1INH and the bradykinin B2 receptor.
Main Results:
- C1INH-deficient mice exhibited increased vascular permeability, which was reversed by C1INH, DX88, and Hoe140.
- Mice lacking both C1INH and the bradykinin B2 receptor showed no increased vascular permeability.
- These findings strongly implicate bradykinin in HAE-related vascular permeability.
Conclusions:
- Angioedema pathogenesis is significantly mediated by bradykinin.
- C1INH plays a crucial role in modulating vascular permeability and inflammatory responses.
- The developed mouse model is valuable for evaluating novel HAE treatments.
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