Mouse model for hereditary hemorrhagic telangiectasia has a generalized vascular abnormality
Autor: | Austin G. Diamond, Helen M. Arthur, R. G. Charlton, James V. Soames, John Burn, Evelyn Torsney |
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Rok vydání: | 2003 |
Předmět: |
Pathology
medicine.medical_specialty Angiogenesis Vascular Cell Adhesion Molecule-1 Receptors Cell Surface Angioma Pathogenesis Mice Antigens CD Physiology (medical) medicine Animals Telangiectasia biology Vascular disease business.industry Endoglin Dermis medicine.disease Phenotype Immunohistochemistry Mice Mutant Strains biology.protein Blood Vessels Telangiectasia Hereditary Hemorrhagic medicine.symptom Cardiology and Cardiovascular Medicine business Elastin Gene Deletion |
Zdroj: | Circulation. 107(12) |
ISSN: | 1524-4539 |
Popis: | Background— Mutations in endoglin or activin like kinase-1, both involved in the endothelial transforming growth factor-β signaling pathway, cause the autosomal dominant bleeding disorder hereditary hemorrhagic telangiectasia. We and others have reported mouse models for this disease that share the characteristic phenotype of dilated vessels and sporadic hemorrhage. The reasons for the variable phenotype in hereditary hemorrhagic telangiectasia are not understood. Methods and Results— After a detailed immunohistochemical analysis of 129/Ola mice, which are heterozygous for a targeted deletion in the endoglin gene, we observed intrinsic abnormalities in the vascular walls throughout the cutaneous vasculature. Postcapillary venules were dilated, and up to 70% of the vascular wall had no smooth muscle cells. The supporting layers of collagens and elastin were irregular, with thin areas, adding to the fragility of these vessels. A variable hemorrhagic phenotype was observed in which local bleeding is associated not only with fragile vessels but also with regions of inflammation. Conclusions— These findings have relevance to our understanding of the molecular basis of vascular integrity in a wide range of diseases. |
Databáze: | OpenAIRE |
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