Soluble FLT1 Gene Therapy Alleviates Brain Arteriovenous Malformation Severity.

ABSTRACT:

Background and purpose

Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current therapies are associated with high morbidities. Excessive vascular endothelial growth factor has been implicated in bAVM pathophysiology. Because soluble FLT1 binds to vascular endothelial growth factor with high affinity, we tested intravenous delivery of an adeno-associated viral vector serotype-9 expressing soluble FLT1 (AAV9-sFLT1) to alleviate the bAVM phenotype.

Methods

Two mouse models were used. In model 1, bAVM was induced in R26CreER;Eng^2f/2f mice through global Eng gene deletion and brain focal angiogenic stimulation; AAV2-sFLT02 (an AAV expressing a shorter form of sFLT1) was injected into the brain at the time o

SUBMITTER: Zhu W 

PROVIDER: S-EPMC5404983 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature