The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases
Open accessAbstract
Cerebral cavernous malformation (CCM) is a common vascular dysplasia that affects both systemic and central nervous system blood vessels. Loss of function mutations in the CCM2 gene cause CCM. Here we show that targeted disruption of Ccm2 in mice results in failed lumen formation and early embryonic death through an endothelial cell autonomous mechanism. We show that CCM2 regulates endothelial cytoskeletal architecture, cell-to-cell interactions and lumen formation. Heterozygosity at Ccm2, a genotype equivalent to that in human CCM, results in impaired endothelial barrier function. On the basis of our biochemical studies indicating that loss of CCM2 results in activation of RHOA GTPase, we rescued the cellular phenotype and barrier function in heterozygous mice with simvastatin, a drug known to inhibit Rho GTPases. These data offer the prospect for pharmacological treatment of a human vascular dysplasia with a widely available and safe drug.
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Cites
Risau, W. (1997) · Nature · doi:10.1038/386671a0 · Cited by 5,727
Rho GTPases Control Polarity, Protrusion, and Adhesion during Cell Movement
Nobes, C. D., & Hall, A. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.144.6.1235 · Cited by 1,445
Tie2-Cre Transgenic Mice: A New Model for Endothelial Cell-Lineage Analysis in Vivo
Kisanuki, Y. Y., Hammer, R. E., Miyazaki, J.-I., Williams, S. C., Richardson, J. A., & Yanagisawa, M. (2001) · Developmental Biology · doi:10.1006/dbio.2000.0106 · Cited by 1,241
Sounding the Alarm: Protein Kinase Cascades Activated by Stress and Inflammation
Kyriakis, J. M., & Avruch, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24313 · Cited by 1,084
Natural history of the cavernous angioma
Robinson, J. R., Awad, I. A., & Little, J. R. (1991) · Journal of Neurosurgery · doi:10.3171/jns.1991.75.5.0709 · Cited by 972
Endothelial tubes assemble from intracellular vacuoles in vivo
Kamei, M., Brian Saunders, W., Bayless, K. J., Dye, L., Davis, G. E., & Weinstein, B. M. (2006) · Nature · doi:10.1038/nature04923 · Cited by 522
Self-citationTruncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas
Couteulx, S. L.-L., Jung, H. H., Labauge, P., Houtteville, J.-P., Lescoat, C., Cecillon, M., Marechal, E., Joutel, A., Bach, J.-F., & Tournier-Lasserve, E. (1999) · Nature Genetics · doi:10.1038/13815 · Cited by 482
Hirose, M., Ishizaki, T., Watanabe, N., Uehata, M., Kranenburg, O., Moolenaar, W. H., Matsumura, F., Maekawa, M., Bito, H., & Narumiya, S. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.7.1625 · Cited by 468
Rho and Rac but not Cdc42 regulate endothelial cell permeability
Wójciak-Stothard, B., Potempa, S., Eichholtz, T., & Ridley, A. J. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.7.1343 · Cited by 465
Mutations within the Programmed Cell Death 10 Gene Cause Cerebral Cavernous Malformations
Bergametti, F., Denier, C., Labauge, P., Arnoult, M., Boetto, S., Clanet, M., Coubes, P., Echenne, B., Ibrahim, R., Irthum, B., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/426952 · Cited by 450
Cited by
EndMT contributes to the onset and progression of cerebral cavernous malformations
Maddaluno, L., Rudini, N., Cuttano, R., Bravi, L., Giampietro, C., Corada, M., Ferrarini, L., Orsenigo, F., Papa, E., Boulday, G., et al. (2013) · Nature · doi:10.1038/nature12207 · Cited by 486
Epac: Defining a New Mechanism for cAMP Action
Gloerich, M., & Bos, J. L. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105714 · Cited by 473
Mechanisms of Vessel Branching: Filopodia on Endothelial Tip Cells Lead the Way
De Smet, F., Segura, I., De Bock, K., Hohensinner, P. J., & Carmeliet, P. (2009) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.109.185165 · Cited by 397
Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity
Stockton, R. A., Shenkar, R., Awad, I. A., & Ginsberg, M. H. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091258 · Cited by 351
Cerebral cavernous malformations arise from endothelial gain of MEKK3–KLF2/4 signalling
Zhou, Z., Tang, A. T., Wong, W.-Y., Bamezai, S., Goddard, L. M., Shenkar, R., Zhou, S., Yang, J., Wright, A. C., Foley, M., et al. (2016) · Nature · doi:10.1038/nature17178 · Cited by 332
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Metadata
- Authors
- Whitehead, K. J., Chan, A. C., Navankasattusas, S., Koh, W., London, N. R., Ling, J., Mayo, A. H., Drakos, S. G., Jones, C. A., Zhu, W., Marchuk, D. A., Davis, G. E., & Li, D. Y.
- Venue
- Nature Medicine
- Published
- 2009-01-18
- Volume
- 15
- Issue
- 2
- Pages
- 177-184
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2058599028
- Cited by
- 377
- References
- 37
- FWCI
- 20.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Whitehead, K. J., Chan, A. C., Navankasattusas, S., Koh, W., London, N. R., Ling, J., Mayo, A. H., Drakos, S. G., Jones, C. A., Zhu, W., Marchuk, D. A., Davis, G. E., & Li, D. Y. (2009). The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nature Medicine. https://doi.org/10.1038/nm.1911
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