Receptors of the Notch signaling pathway are associated with hemorrhage of brain arteriovenous malformations

Abstract

Brain arteriovenous malformation (bAVM) is currently one of the most common cerebral vascular diseases, which result in severe clinical outcomes. The Notch signaling pathway is involved in vasculogenesis and angiogenesis, as well as vascular remodeling and arteriovenous differentiation in multiple diseases. Although there are previous studies on the correlation between bAVM and the Notch signaling pathway, none of these studies have elucidated whether abnormal expression levels of the key factors in this pathway are associated with hemorrhage of bAVMs. The present study compared the expression levels of NOTCH1, NOTCH4 and two of their binding ligand genes, DLL4 and JAGGED1, in bAVM nidus and normal superficial temporal arteries (STAs) by quantitative polymerase chain reaction and immunohistochemical staining. The bAVM patient group was further stratified into hemorrhage and non-hemorrhage groups to determine the expression levels of the four genes. It was observed that the expression levels of NOTCH1 and NOTCH4 were significantly increased in the bAVM cohort as compared with that of the control group. DLL4 and JAGGED1 exhibited the same expression levels in bAVMs and STAs. In addition, increased expression levels of NOTCH1 were observed in the hemorrhage group compared with that of the non-hemorrhage group. However, the expression levels of NOTCH4, DLL4 and JAGGED1 showed no significant differences between the hemorrhage and non-hemorrhage groups. Abnormal NOTCH1 expression was detected in the hemorrhage group, but other ligands of the Notch signaling pathway remained the same, suggesting that, although NOTCH1 was upregulated in patients with bAVM, other ligands in this signaling pathway may be irrelevant to hemorrhage.