REFERENCES
1. Wong JH, Awad IA, Kim JH. Ultrastructural pathological features of cerebrovascular malformations: a preliminary report. Neurosurgery 2000;46:1454-9.
2. Padarti A, Zhang J. Recent advances in cerebral cavernous malformation research. Vessel Plus 2018;2:21.
3. Awad IA, Polster SP. Cavernous angiomas: deconstructing a neurosurgical disease. J Neurosurg 2019;131:1-13.
4. Xie MG, Li D, Guo FZ, et al. Brainstem cavernous malformations: surgical indications based on natural history and surgical outcomes. World Neurosurg 2018;110:55-63.
5. Flemming KD, Graff-Radford J, Aakre J, et al. Population-based prevalence of cerebral cavernous malformations in older adults: Mayo Clinic Study of Aging. JAMA Neurol 2017;74:801-5.
6. Flemming KD, Lanzino G. Cerebral cavernous malformation: what a practicing clinician should know. Mayo Clin Proc 2020;95:2005-20.
7. Zabramski JM, Wascher TM, Spetzler RF, et al. The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 1994;80:422-32.
8. Spiegler S, Rath M, Paperlein C, Felbor U. Cerebral cavernous malformations: an update on prevalence, molecular genetic analyses, and genetic counselling. Mol Syndromol 2018;9:60-9.
9. Denier C, Labauge P, Bergametti F, et al. Société Française de Neurochirurgie. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol 2006;60:550-6.
10. Riant F, Cecillon M, Saugier-Veber P, Tournier-Lasserve E. CCM molecular screening in a diagnosis context: novel unclassified variants leading to abnormal splicing and importance of large deletions. Neurogenetics 2013;14:133-41.
11. Akers A, Al-Shahi Salman R, A Awad I, et al. Synopsis of guidelines for the clinical management of cerebral cavernous malformations: consensus recommendations based on systematic literature review by the angioma alliance scientific advisory board clinical experts panel. Neurosurgery 2017;80:665-80.
12. Su VL, Calderwood DA. Signalling through cerebral cavernous malformation protein networks. Open Biol 2020;10:200263.
13. Retta SF, Glading AJ. Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: two sides of the same coin. Int J Biochem Cell Biol 2016;81:254-70.
14. Retta SF, Perrelli A, Trabalzini L, Finetti F. From genes and mechanisms to molecular-targeted therapies: the long climb to the cure of cerebral cavernous malformation (CCM) disease. Methods Mol Biol 2020;2152:3-25.
15. Maddaluno L, Rudini N, Cuttano R, et al. EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature 2013;498:492-6.
16. Zhou Z, Tang AT, Wong WY, et al. Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. Nature 2016;532:122-6.
17. Lopez-Ramirez MA, Fonseca G, Zeineddine HA, et al. Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations. J Exp Med 2017;214:3331-46.
18. Zhou Z, Rawnsley DR, Goddard LM, et al. The cerebral cavernous malformation pathway controls cardiac development via regulation of endocardial MEKK3 signaling and KLF expression. Dev Cell 2015;32:168-80.
19. Glading A, Han J, Stockton RA, Ginsberg MH. KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J Cell Biol 2007;179:247-54.
20. Glading AJ, Ginsberg MH. Rap1 and its effector KRIT1/CCM1 regulate beta-catenin signaling. Dis Model Mech 2010;3:73-83.
21. Antognelli C, Trapani E, Delle Monache S, et al. KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that sensitizes cells to oxidative stress: Implication for Cerebral Cavernous Malformation disease. Free Radic Biol Med 2018;115:202-18.
22. Goitre L, DiStefano PV, Moglia A, et al. Up-regulation of NADPH oxidase-mediated redox signaling contributes to the loss of barrier function in KRIT1 deficient endothelium. Sci Rep 2017;7:8296.
23. Goitre L, De Luca E, Braggion S, et al. KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun. Free Radic Biol Med 2014;68:134-47.
24. Chohan MO, Marchiò S, Morrison LA, et al. Emerging pharmacologic targets in cerebral cavernous malformation and potential strategies to alter the natural history of a difficult disease: a Review. JAMA Neurol 2019;76:492-500.
25. Gault J, Shenkar R, Recksiek P, Awad IA. Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion. Stroke 2005;36:872-4.
26. Akers AL, Johnson E, Steinberg GK, Zabramski JM, Marchuk DA. Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis. Hum Mol Genet 2009;18:919-30.
27. McDonald DA, Shi C, Shenkar R, et al. Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis. Hum Mol Genet 2014;23:4357-70.
28. Riant F, Bergametti F, Ayrignac X, Boulday G, Tournier-Lasserve E. Recent insights into cerebral cavernous malformations: the molecular genetics of CCM. FEBS J 2010;277:1070-5.
30. Rath M, Pagenstecher A, Hoischen A, Felbor U. Postzygotic mosaicism in cerebral cavernous malformation. J Med Genet 2020;57:212-6.
31. Gault J, Awad IA, Recksiek P, et al. Cerebral cavernous malformations: somatic mutations in vascular endothelial cells. Neurosurgery 2009;65:138-44; discussion 144.
32. Pagenstecher A, Stahl S, Sure U, Felbor U. A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. Hum Mol Genet 2009;18:911-8.
33. Detter MR, Snellings DA, Marchuk DA. Cerebral cavernous malformations develop through clonal expansion of mutant endothelial cells. Circ Res 2018;123:1143-51.
34. Malinverno M, Maderna C, Abu Taha A, et al. Endothelial cell clonal expansion in the development of cerebral cavernous malformations. Nat Commun 2019;10:2761.
35. Louvi A, Chen L, Two AM, Zhang H, Min W, Günel M. Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology. Proc Natl Acad Sci U S A 2011;108:3737-42.
36. Wang K, Zhang H, He Y, et al. Mural cell-specific deletion of cerebral cavernous malformation 3 in the brain induces cerebral cavernous malformations. Arterioscler Thromb Vasc Biol 2020;40:2171-86.
37. Lopez-Ramirez MA, Soliman SI, Hale P, et al. Non cell-autonomous effect of astrocytes on cerebral cavernous malformations. BioRxiv 2021; doi: 10.1101/2021.01.29.428891.
38. Finetti F, Schiavo I, Ercoli J, et al. KRIT1 loss-mediated upregulation of NOX1 in stromal cells promotes paracrine pro-angiogenic responses. Cell Signal 2020;68:109527.
39. Chapman EM, Lant B, Ohashi Y, et al. A conserved CCM complex promotes apoptosis non-autonomously by regulating zinc homeostasis. Nat Commun 2019;10:1791.
40. Wüstehube J, Bartol A, Liebler SS, et al. Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A 2010;107:12640-5.
41. DiStefano PV, Kuebel JM, Sarelius IH, Glading AJ. KRIT1 protein depletion modifies endothelial cell behavior via increased vascular endothelial growth factor (VEGF) signaling. J Biol Chem 2014;289:33054-65.
42. Baev NI, Awad IA. Endothelial cell culture from human cerebral cavernous malformations. Stroke 1998;29:2426-34.
43. Zhao Y, Tan YZ, Zhou LF, Wang HJ, Mao Y. Morphological observation and in vitro angiogenesis assay of endothelial cells isolated from human cerebral cavernous malformations. Stroke 2007;38:1313-9.
44. Glading AJ, Finetti F, Trabalzini L. Disease models in cerebral cavernous malformations. Drug Discov Today Dis Model 2020;31:21-9.
45. Wang K, Zhou HJ, Wang M. CCM3 and cerebral cavernous malformation disease. Stroke Vasc Neurol 2019;4:67-70.
46. Jenny Zhou H, Qin L, Zhang H, et al. Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation. Nat Med 2016;22:1033-42.
47. Sartages M, Floridia E, García-Colomer M, et al. High levels of receptor tyrosine kinases in ccm3-deficient cells increase their susceptibility to tyrosine kinase inhibition. Biomedicines 2020;8:624.
48. DiStefano PV, Glading AJ. VEGF signalling enhances lesion burden in KRIT1 deficient mice. J Cell Mol Med 2020;24:632-9.
49. Schulz GB, Wieland E, Wüstehube-Lausch J, et al. Cerebral cavernous malformation-1 protein controls DLL4-Notch3 signaling between the endothelium and pericytes. Stroke 2015;46:1337-43.
50. You C, Zhao K, Dammann P, et al. EphB4 forward signalling mediates angiogenesis caused by CCM3/PDCD10-ablation. J Cell Mol Med 2017;21:1848-58.
51. Whitehead KJ, Plummer NW, Adams JA, Marchuk DA, Li DY. Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Development 2004;131:1437-48.
52. Bravi L, Malinverno M, Pisati F, et al. Endothelial cells lining sporadic cerebral cavernous malformation cavernomas undergo endothelial-to-mesenchymal transition. Stroke 2016;47:886-90.
53. Dejana E, Hirschi KK, Simons M. The molecular basis of endothelial cell plasticity. Nat Commun 2017;8:14361.
54. Fisher OS, Liu W, Zhang R, et al. Structural basis for the disruption of the cerebral cavernous malformations 2 (CCM2) interaction with Krev interaction trapped 1 (KRIT1) by disease-associated mutations. J Biol Chem 2015;290:2842-53.
55. Cullere X, Plovie E, Bennett PM, MacRae CA, Mayadas TN. The cerebral cavernous malformation proteins CCM2L and CCM2 prevent the activation of the MAP kinase MEKK3. Proc Natl Acad Sci U S A 2015;112:14284-9.