The roles of endoglin gene in cerebrovascular diseases.

Endoglin (ENG, also known as CD105) is a transforming growth factor β (TGFβ) associated receptor and is required for both vasculogenesis and angiogenesis. Angiogenesis is important in the development of cerebral vasculature and in the pathogenesis of cerebral vascular diseases. ENG is an essential component of the endothelial nitric oxide synthase activation complex. Animal studies showed that ENG deficiency impairs stroke recovery. ENG deficiency also impairs the regulation of vascular tone, which contributes to the pathogenesis of brain arteriovenous malformation (bAVM) and vasospasm. In human, functional haploinsufficiency of gene causes type I hereditary hemorrhagic telangiectasia (HHT1), an autosomal dominant disorder. Compared to normal population, HHT1 patients have a higher prevalence of AVM in multiple organs including the brain. Vessels in bAVM are fragile and tend to rupture, causing hemorrhagic stroke. High prevalence of pulmonary AVM in HHT1 patients are associated with a higher incidence of paradoxical embolism in the cerebral circulation causing ischemic brain injury. Therefore, HHT1 patients are at risk for both hemorrhagic and ischemic stroke. This review summarizes the possible mechanism of ENG in the pathogenesis of cerebrovascular diseases in experimental animal models and in patients.