De novo cerebrovascular malformation in the adult mouse after endothelial Alk1 deletion and angiogenic stimulation
| Autor: | Chen, Wanqiu, Sun, Zhengda, Han, Zhenying, Jun, Kristine, Camus, Marine, Wankhede, Mamta, Mao, Lei, Arnold, Tom, Young, William L, Su, Hua |
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| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
AVM (arteriovenous malformation) intracranial Antimetabolites Activin Receptors Clinical Sciences Type I Genetically Modified Antineoplastic Agents Cardiorespiratory Medicine and Haematology Cardiovascular Type II hereditary hemorrhagic Adenoviridae Mice models Animals 2.1 Biological and endogenous factors animal telangiectasia Aetiology Cell Proliferation Central Nervous System Vascular Malformations Pediatric Neurology & Neurosurgery Hormonal Organisms Neurosciences Endothelial Cells Exons Tamoxifen Bromodeoxyuridine type 2 Congenital Structural Anomalies Angiogenesis Inducing Agents Gene Deletion |
| Zdroj: | Stroke, vol 45, iss 3 |
| Popis: | Background and purposeIn humans, activin receptor-like kinase 1 (Alk1) deficiency causes arteriovenous malformations (AVMs) in multiple organs, including the brain. Focal Alk1 pan-cellular deletion plus vascular endothelial growth factor stimulation induces brain AVMs in the adult mouse. We hypothesized that deletion of Alk1 in endothelial cell (EC) alone plus focal vascular endothelial growth factor stimulation is sufficient to induce brain AVM in the adult mouse.MethodsFocal angiogenesis was induced in the brain of 8-week-old Pdgfb-iCreER;Alk1(2f/2f) mice by injection of adeno-associated viral vectors expressing vascular endothelial growth factor. Two weeks later, EC-Alk1 deletion was induced by tamoxifen treatment. Vascular morphology was analyzed, and EC proliferation and dysplasia index (number of vessels with diameter>15 μm per 200 vessels) were quantified 10 days after tamoxifen administration.ResultsTangles of enlarged vessels resembling AVMs were present in the brain angiogenic region of tamoxifen-treated Pdgfb-iCreER;Alk1(2f/2f) mice. Induced brain AVMs were marked by increased dysplasia index (P |
| Databáze: | OpenAIRE |
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