Minimal homozygous endothelial deletion of Eng with VEGF stimulation is sufficient to cause cerebrovascular dysplasia in the adult mouse.
Abstract
Brain arteriovenous malformations (bAVMs) represent a high risk for hemorrhagic stroke, leading to significant neurological morbidity and mortality in young adults. The etiopathogenesis of bAVM remains unclear. Research progress has been hampered by the lack of animal models. Hereditary Hemorrhagic Telangiectasia (HHT) patients with haploinsufficiency of endoglin (ENG, HHT1) or activin receptor-like kinase 1 (ALK1, HHT2) have a higher incidence of bAVM than the general population. We previously induced cerebrovascular dysplasia in the adult mouse that resembles human bAVM through Alk1 deletion plus vascular endothelial growth factor (VEGF) stimulation. We hypothesized that Eng deletion plus VEGF stimulation would induce a similar degree of cerebrovascular dysplasia as the Alk1-deleted brain. Ad-Cre (an adenoviral vector expressing Cre recombinase) and AAV-VEGF (an adeno-associated viral vector expressing VEGF) were co-injected into the basal ganglia of 8- to 10-week-old Eng(2f/2f) (exons 5 and 6 flanked by loxP sequences), Alk1(2f/2f) (exons 4-6 flanked by loxP sequences) and wild-type (WT) mice. Vascular density, dysplasia index, and gene deletion efficiency were analyzed 8 weeks later. AAV-VEGF induced a similar degree of ang...Continue Reading
References
Citations
Novel brain arteriovenous malformation mouse models for type 1 hereditary hemorrhagic telangiectasia
Related Concepts
Related Feeds
Cavernous Hemangioma
Cavernous hemangioma is a blood vessel defect or benign tumor that leads to leakage of blood to the surrounding tissues. This can occur in several organs including the brain, which can lead to seizures. Discover the latest research on cavernous hemangiomas here.
Arterial-Venous in Development & Disease
Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.
Basal Ganglia
Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.
Basal Ganglia Cerebrovascular Disease
Basal ganglia cerebrovascular disease is a condition where the blood vessels in the basal ganglia are damaged or malfunction. Discover the latest research on basal ganglia cerebrovascular disease here.