Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis.
OBJECTIVE
Molecular genetic studies of cerebral cavernous malformation (CCM) have identified three loci, CCM1-3, that can lead to CCM when mutated. Examination of the CCM1 locus established KRIT1 (Krev1 Interaction Trapped genre 1) as the CCM1 gene. Despite the identification of KRIT1 as the gene mutated in CCM1, little has been learned regarding its function. The authors recently demonstrated specific KRIT1 expression in endothelial cells. Based on this result and the fact that the CCM phenotype features defects in microvasculature, we hypothesized that KRIT1 may take an active part in normal angiogenesis.


METHODS
In this study, the authors investigated the spatial and temporal expression of KRIT1 during normal vessel development and maturation by examining KRIT1 protein in both in vitro and in vivo angiogenic systems with the use of postconfluent endothelial cell cultures along with placental tissues from different developmental stages.


CONCLUSIONS
The results demonstrate that KRIT1 is expressed during capillary-like tube formation in the early stages of angiogenesis in vitro. Histological examination of placental tissue, a well-established in vivo model of angiogenesis, shows KRIT1 expression in active angiogenic and vasculogenic areas of the immature placental villi. As the placenta matures, KRIT1 expression is restricted to microvascular and small arterial endothelial cells with little or no expression seen in the intima of large vessels. It can therefore be concluded that KRIT1 is expressed during early angiogenesis by endothelial cells and may play a key role in vessel formation and/or development.
Yale Neurovascular Surgery Program and Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Ozlem
O
Guzeloglu-Kayisli
Umit A
UA
Kayisli
Nduka M
NM
Amankulor
Jennifer R
JR
Voorhees
Ozgun
O
Gokce
Michael L
ML
DiLuna
Maxwell S H
MS
Laurans
Guven
G
Luleci
Murat
M
Gunel
D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002478:Cells, Cultured; D020785:Central Nervous System Vascular Malformations / Q000235:genetics*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D000075927:KRIT1 Protein; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016296:Mutagenesis; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010784:Photomicrography; D010920:Placenta / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins