Abstract
Up-regulation of Notch4 was observed in the endothelial cells in the arteriovenous malformations (AVMs) in mice. However, whether Notch4 is also involved in brain AVMs in humans remains unclear. Here, we performed immunohistochemistry on normal brain vascular tissue and surgically resected brain AVMs and found that Notch4 was up-regulated in the subset of abnormal vessels of the brain AVM nidus, compared with control brain vascular tissue. Two-photon confocal images show that Notch4 was expressed not only in the endothelial but also in the smooth muscle cells of the vascular wall in brain AVMs. Western blotting shows that Notch4 was activated in brain AVMs, but not in middle cerebral artery of normal human brain, which was confirmed by immunostaining. Our findings suggest a possible contribution of Notch4 signalling to the development of brain AVMs in human.
Highlights
Brain arteriovenous malformations (AVMs) are morphological abnormalities characterized by direct communication between arteries and veins without intervening capillary beds
We found that Notch4 expression was significantly increased in the cells of some abnormal vessel walls of brain AVMs, suggesting that Notch4 was selectively expressed in the subset of brain AVM nidus
We found that Notch4 was activated in endothelial and smooth muscle cells (SMC) of human brain AVMs
Summary
Brain arteriovenous malformations (AVMs) are morphological abnormalities characterized by direct communication between arteries and veins without intervening capillary beds. Arteriovenous malformations are generally thought to be congenital vascular anomalies that arise as a result of the abnormal development of blood vessels during the early embryonic period [1]. Notch signalling in link with AVMs was initially suggested based on the findings that Notch signalling is required for the proper development of arterial and venous blood vessels, as mice with defects in. The survival of Notch4-deficient mice shows that Notch is dispensable for vascular development [8], while expression of an activated form of Notch within the endothelium disrupts normal vascular development [9, 10].
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