10.6084/m9.figshare.4771579.v1
Liu H.
Liu
H.
Rigamonti D.
Rigamonti
D.
Badr A.
Badr
A.
Zhang J.
Zhang
J.
Supplementary Material for: Ccm1 Regulates Microvascular Morphogenesis during Angiogenesis
Karger Publishers
2017
Angiogenesis
Cerebral cavernous malformation
CCM1
Intersegmental vessels
Vacuole/lumen formation
Vascular endothelial cells
2017-03-21 13:50:16
Dataset
https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Ccm1_Regulates_Microvascular_Morphogenesis_during_Angiogenesis/4771579
<p>Cerebral cavernous malformations (CCMs) are characterized by
abnormally dilated intracranial capillaries that have a propensity to
bleed. The development of some CCMs in humans has been attributed to
mutations in CCM1 and CCM2 genes. In animal models, major cardiovascular
defects caused by both gene mutations have been observed. However, the
effects of the loss of Ccm function on the microvasculature in animal
models are less defined. Using high-resolution imaging in vivo, we
demonstrated that the loss of Ccm1 in zebrafish embryos leads to failed
microvascular lumenization during angiogenesis due to impaired
intraendothelial vacuole formation and fusion. No developmental changes
during vasculogenesis and the initial stage of angiogenesis were
observed, being in contrast to prior reports. In vivo zebrafish studies
were further substantiated by in vitro findings in human endothelial
cells that elucidated the biochemical pathways of CCM1 deficiency. We
found that CCM1 regulates angiogenic microvascular lumen formation
through Rac1 small GTPase. In summary, Ccm1 has been identified as a key
angiogenic modulator in microvascular tubulogenesis. Additionally, the
microvascular pathology observed in developing Ccm1 mutant zebrafish
embryos mirrors that seen in human CCM lesions, suggesting that
zebrafish might provide a superior animal model to study the
pathogenesis of human CCM.</p>