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Patients with mutations in any of three\n                    <jats:italic>CCM<\/jats:italic>\n                    genes may suffer from neurological deficits and even hemorrhagic stroke. The three CCM proteins are structurally unrelated and assemble into the CCM complex that forms scaffolds associated with junctional complexes and the actomyosin cytoskeleton. Recent work points to a dual role of the CCM complex in structural scaffolding and mechanosensitive signal transduction. In this review, we highlight recent advances examining the CCM complex\u2019s role in organizing various multi-protein interactions and facilitating mechanosensitive signaling that regulates endothelial cell behavior. Importantly, accumulating evidence emphasizes the impact of hemodynamic forces on CCM signaling, pointing to distinct mechanisms in arterial versus venous vessels. Surprisingly, the loss of CCM proteins has vasoprotective effects in arteries but pathological effects in veins and small capillaries. Understanding CCM scaffolds that integrate structural support with mechanosensitive signaling is fundamental to deciphering the molecular mechanisms that underlie physiological versus pathological outcomes within the vasculature. This knowledge advances the development of targeted therapeutic strategies aimed at restoring endothelial integrity and normal vascular function, particularly by modulating signaling pathways influenced by hemodynamic forces.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2025-0246","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T14:18:52Z","timestamp":1772288332000},"page":"247-258","source":"Crossref","is-referenced-by-count":2,"title":["CCM scaffolds at the frontier of biomechanics: their roles in vascular physiology and disease"],"prefix":"10.1515","volume":"407","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2384-1537","authenticated-orcid":false,"given":"Claudia Jasmin","family":"R\u00f6del","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Biology, Potsdam University , Karl-Liebknecht-Stra\u00dfe 24-25, D-14476 Potsdam , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-3841","authenticated-orcid":false,"given":"Salim","family":"Abdelilah-Seyfried","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biology, Potsdam University , Karl-Liebknecht-Stra\u00dfe 24-25, D-14476 Potsdam , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"2026080805591994593_j_hsz-2025-0246_ref_001","doi-asserted-by":"crossref","unstructured":"Abdelilah-Seyfried, S., Tournier-Lasserve, E., and Derry, W.B. (2020). Blocking signalopathic events to treat cerebral cavernous malformations. Trends Mol. Med. 26: 1\u201314, https:\/\/doi.org\/10.1016\/j.molmed.2020.03.003.","DOI":"10.1016\/j.molmed.2020.03.003"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_002","doi-asserted-by":"crossref","unstructured":"Anantharam, A. and Kreutzberger, A.J.B. (2019). Unraveling the mechanisms of calcium-dependent secretion. J.\u00a0Gen. Physiol. 151: 417\u2013434, https:\/\/doi.org\/10.1085\/jgp.201812298.","DOI":"10.1085\/jgp.201812298"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_003","doi-asserted-by":"crossref","unstructured":"Ayata, C., Kim, H., Morrison, L., Liao, J.K., Gutierrez, J., Lopez-Toledano, M., Carrazana, E., Rabinowicz, A.L., and Awad, I.A. (2024). Role of Rho-associated kinase in the pathophysiology of cerebral cavernous malformations. Neurol. Genet. 10: e200121, https:\/\/doi.org\/10.1212\/NXG.0000000000200121.","DOI":"10.1212\/NXG.0000000000200121"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_004","doi-asserted-by":"crossref","unstructured":"Baeyens, N., Mulligan-Kehoe, M.J., Corti, F., Simon, D.D., Ross, T.D., Rhodes, J.M., Wang, T.Z., Mejean, C.O., Simons, M., Humphrey, J., et al.. (2014). Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proc. Natl. Acad. Sci. USA 111: 17308\u201317313, https:\/\/doi.org\/10.1073\/pnas.1413725111.","DOI":"10.1073\/pnas.1413725111"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_005","doi-asserted-by":"crossref","unstructured":"Ball, N.J., Ghimire, S., Follain, G., Pajari, A.O., Wurzinger, D., Vaitkevi\u010di\u016bt\u0117, M., Cowell, A.R., Berki, B., Ivaska, J., Paatero, I., et al.. (2024). TLNRD1 is a CCM complex component and regulates endothelial barrier integrity. 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Res. 115: 32\u201343, https:\/\/doi.org\/10.1161\/CIRCRESAHA.115.303883.","DOI":"10.1161\/CIRCRESAHA.115.303883"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_027","doi-asserted-by":"crossref","unstructured":"Kleaveland, B., Zheng, X., Liu, J.J., Blum, Y., Tung, J.J., Zou, Z., Chen, M., Guo, L., Lu, M.M., Zhou, D., et al.. (2009). Regulation of cardiovascular development and integrity by the heart of glasscerebral cavernous malformation protein pathway. Nat. Med. 15: 169\u2013176, https:\/\/doi.org\/10.1038\/nm.1918.","DOI":"10.1038\/nm.1918"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_028","doi-asserted-by":"crossref","unstructured":"Laberge-le Couteulx, S.L., Jung, H.H., Labauge, P., Houtteville, J.-P., Lescoat, C., Cecillon, M., Marechal, E., Joutel, A., Bach, J.-F., and Tournier-Lasserve, E. (1999). Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat. Genet. 23: 189\u2013193, https:\/\/doi.org\/10.1038\/13815.","DOI":"10.1038\/13815"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_029","doi-asserted-by":"crossref","unstructured":"Lai, C.C., Nelsen, B., Frias-Anaya, E., Gallego-Gutierrez, H., Orecchioni, M., Herrera, V., Ortiz, E., Sun, H., Mesarwi, O.A., Ley, K., et al.. (2022). Neuroinflammation plays a critical role in cerebral cavernous malformation disease. Circ. Res. 131: 909\u2013925, https:\/\/doi.org\/10.1161\/CIRCRESAHA.122.321129.","DOI":"10.1161\/CIRCRESAHA.122.321129"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_030","doi-asserted-by":"crossref","unstructured":"Liquori, C.L., Berg, M.J., Siegel, A.M., Huang, E., Zawistowski, J.S., Stoffer, T., Verlaan, D., Balogun, F., Hughes, L., Leedom, T.P., et al.. (2003). Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am. J.\u00a0Hum. Genet. 73: 1459\u20131464, https:\/\/doi.org\/10.1086\/380314.","DOI":"10.1086\/380314"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_031","doi-asserted-by":"crossref","unstructured":"Lisowska, J., R\u00f6del, C.J., Manet, S., Miroshnikova, Y.A., Boyault, C., Planus, E., De Mets, R., Lee, H.H., Destaing, O., Mertani, H., et al.. (2018). The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity. J.\u00a0Cell Sci. 131, https:\/\/doi.org\/10.1242\/JCS.216093.","DOI":"10.1242\/jcs.216093"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_032","doi-asserted-by":"crossref","unstructured":"Liu, W., Draheim, K.M., Zhang, R., Calderwood, D.A., and Boggon, T.J. (2013). Mechanism for KRIT1 release of ICAP1-mediated suppression of integrin activation. Mol. 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FASEB BioAdvances 3: 334\u2013355, https:\/\/doi.org\/10.1096\/fba.2020-00141.","DOI":"10.1096\/fba.2020-00141"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_035","doi-asserted-by":"crossref","unstructured":"Lu, J., Hu, Z., Deng, Y., Wu, Q., Wu, M., and Song, H. (2021). MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway. J.\u00a0Biol. Chem. 296: 100400, https:\/\/doi.org\/10.1016\/j.jbc.2021.100400.","DOI":"10.1016\/j.jbc.2021.100400"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_036","doi-asserted-by":"crossref","unstructured":"Macek Jilkova, Z., Lisowska, J., Manet, S., Verdier, C., Deplano, V., Geindreau, C., Faurobert, E., Albiges-Rizo, C., and Duperray, A. (2014). CCM proteins control endothelial \u03b21 integrin dependent response to shear stress. Biol. 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Commun. 10: 2761, https:\/\/doi.org\/10.1038\/s41467-019-10707-x.","DOI":"10.1038\/s41467-019-10707-x"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_039","doi-asserted-by":"crossref","unstructured":"Meecham, A., McCurdy, S., Frias-Anaya, E., Li, W., Gallego-Gutierrez, H., Ngyuen, P., Li, J.Y.-S., Chien, S., Shyy, J.Y.-J., Ginsberg, M.H., et al.. (2025). Silencing KRIT1 partially reverses the effects of disturbed flow on the endothelial cell transcriptome, https:\/\/doi.org\/10.1101\/2025.03.12.642862.","DOI":"10.3390\/ijms26094340"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_040","doi-asserted-by":"crossref","unstructured":"Miroshnikova, Y.A., Manet, S., Li, X., Wickstr\u00f6m, S.A., Faurobert, E., and Albiges-Rizo, C. (2021). Calcium signaling mediates a biphasic mechanoadaptive response of endothelial cells to cyclic mechanical stretch. Mol. Biol. Cell 32: 1724\u20131736, https:\/\/doi.org\/10.1091\/mbc.E21-03-0106.","DOI":"10.1091\/mbc.E21-03-0106"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_041","doi-asserted-by":"crossref","unstructured":"Nguyen, D.-H.T., Gao, L., Wong, A., and Chen, C.S. (2017). Cdc42 regulates branching in angiogenic sprouting in\u00a0vitro. Microcirculation 24: e12372, https:\/\/doi.org\/10.1111\/micc.12372.","DOI":"10.1111\/micc.12372"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_042","doi-asserted-by":"crossref","unstructured":"Park, S., Lee, H.-Y., Kim, Jayoung, Park, H., Ju, Y.S., Kim, E.-G., and Kim, Jaehong (2021). Cerebral Cavernous Malformation 1 determines YAP\/TAZ signaling-dependent metastatic hallmarks of prostate cancer cells. 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Med. 16: 2827\u20132855, https:\/\/doi.org\/10.1038\/s44321-024-00152-9.","DOI":"10.1038\/s44321-024-00152-9"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_045","doi-asserted-by":"crossref","unstructured":"Qi, C., Bujaroski, R.S., Baell, J., and Zheng, X. (2023). Kinases in cerebral cavernous malformations: pathogenesis and therapeutic targets. Biochim. Biophys. Acta BBA\u00a0\u2013\u00a0Mol. Cell Res. 1870: 119488, https:\/\/doi.org\/10.1016\/j.bbamcr.2023.119488.","DOI":"10.1016\/j.bbamcr.2023.119488"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_046","doi-asserted-by":"crossref","unstructured":"Ren, A.A., Snellings, D.A., Su, Y.S., Hong, C.C., Castro, M., Tang, A.T., Detter, M.R., Hobson, N., Girard, R., Romanos, S., et al.. (2021). PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism. Nature 594, https:\/\/doi.org\/10.1038\/s41586-021-03562-8.","DOI":"10.1038\/s41586-021-03562-8"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_047","doi-asserted-by":"crossref","unstructured":"Renz, M., Otten, C., Faurobert, E., Rudolph, F., Zhu, Y., Boulday, G., Duchene, J., Mickoleit, M., Dietrich, A.-C., Ramspacher, C., et al.. (2015). Regulation of \u03b21 integrin-Klf2-mediated angiogenesis by CCM proteins. Dev. Cell 32: 181\u2013190, https:\/\/doi.org\/10.1016\/j.devcel.2014.12.016.","DOI":"10.1016\/j.devcel.2014.12.016"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_048","doi-asserted-by":"crossref","unstructured":"Richardson, B.T., Dibble, C.F., Borikova, A.L., and Johnson, G.L. (2013). Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling. Biol. 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Nature 626: 799\u2013807, https:\/\/doi.org\/10.1038\/s41586-024-07022-x.","DOI":"10.1038\/s41586-024-07022-x"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_051","doi-asserted-by":"crossref","unstructured":"Shapeti, A., Barrasa-Fano, J., Abdel Fattah, A.R., de Jong, J., Sanz-Herrera, J.A., Pezet, M., Assou, S., de Vet, E., Elahi, S.A., Ranga, A., et al.. (2024). Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth. Nat. Commun. 15: 8660, https:\/\/doi.org\/10.1038\/s41467-024-52866-6.","DOI":"10.1038\/s41467-024-52866-6"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_052","doi-asserted-by":"crossref","unstructured":"Shen, Q., Wu, M.H., and Yuan, S.Y. (2009). Endothelial contractile cytoskeleton and microvascular permeability. 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Biology 10, https:\/\/doi.org\/10.3390\/biology10101041.","DOI":"10.3390\/biology10101041"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_055","doi-asserted-by":"crossref","unstructured":"Snellings, D.A., Hong, C.C., Ren, A.A., Lopez-Ramirez, M.A., Girard, R., Srinath, A., Marchuk, D.A., Ginsberg, M.H., Awad, I.A., and Kahn, M.L. (2021). Cerebral cavernous malformation: from mechanism to therapy. Circ. Res. 129: 195\u2013215, https:\/\/doi.org\/10.1161\/CIRCRESAHA.121.318174.","DOI":"10.1161\/CIRCRESAHA.121.318174"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_056","doi-asserted-by":"crossref","unstructured":"Stamatovic, S.M., Sladojevic, N., Keep, R.F., and Andjelkovic, A.V. (2015). PDCD10 (CCM3) regulates brain endothelial barrier integrity in cerebral cavernous malformation type 3: role of CCM3-ERK1\/2-cortactin cross-talk. Acta Neuropathol. (Berl.): 1\u201320, https:\/\/doi.org\/10.1007\/s00401-015-1479-z.","DOI":"10.1007\/s00401-015-1479-z"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_057","doi-asserted-by":"crossref","unstructured":"Stockton, R.A., Shenkar, R., Awad, I.A., and Ginsberg, M.H. (2010). Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J.\u00a0Exp. Med. 207: 881\u2013896, https:\/\/doi.org\/10.1084\/jem.20091258.","DOI":"10.1084\/jem.20091258"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_058","doi-asserted-by":"crossref","unstructured":"Sun, B., Zhong, F.-J., Xu, C., Li, Y.-M., Zhao, Y.-R., Cao, M.-M., and Yang, L.-Y. (2021). Programmed cell death 10 promotes metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma via PP2Ac-mediated YAP activation. Cell Death Dis. 12: 849, https:\/\/doi.org\/10.1038\/s41419-021-04139-z.","DOI":"10.1038\/s41419-021-04139-z"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_059","doi-asserted-by":"crossref","unstructured":"Suzuki, Y., Giles, W.R., Zamponi, G.W., Kondo, R., Imaizumi, Y., and Yamamura, H. (2024). Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review. Inflamm. Regen. 44: 50, https:\/\/doi.org\/10.1186\/s41232-024-00363-0.","DOI":"10.1186\/s41232-024-00363-0"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_060","doi-asserted-by":"crossref","unstructured":"Swamy, H. and Glading, A.J. (2022). Is location everything? Regulation of the endothelial CCM signaling complex. Front. Cardiovasc. Med. 9: 954780, https:\/\/doi.org\/10.3389\/fcvm.2022.954780.","DOI":"10.3389\/fcvm.2022.954780"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_061","doi-asserted-by":"crossref","unstructured":"Sweet, D.R., Padmanabhan, R., Liao, X., Dashora, H.R., Tang, X., Nayak, L., Jain, R., De Val, S., Vinayachandran, V., and Jain, M.K. (2023). Kr\u00fcppel\u2010like factors orchestrate endothelial gene expression through redundant and non\u2010redundant enhancer networks. J.\u00a0Am. Heart Assoc. 12: e024303, https:\/\/doi.org\/10.1161\/JAHA.121.024303.","DOI":"10.1161\/JAHA.121.024303"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_062","doi-asserted-by":"crossref","unstructured":"Tamargo, I.A., Baek, K.I., Xu, C., Kang, D.W., Kim, Y., Andueza, A., Williams, D., Demos, C., Villa-Roel, N., Kumar, S., et al.. (2024). HEG1 protects against atherosclerosis by regulating stable flow-induced KLF2\/4 expression in endothelial cells. Circulation 149: 1183\u20131201, https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.123.064735.","DOI":"10.1161\/CIRCULATIONAHA.123.064735"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_063","doi-asserted-by":"crossref","unstructured":"Tang, L., Zhou, M., Xu, Y., Peng, B., Gao, Y., and Mo, Y. (2024). Knockdown of CCM3 promotes angiogenesis through activation and nuclear translocation of YAP\/TAZ. Biochem. Biophys. Res. Commun. 701: 149525, https:\/\/doi.org\/10.1016\/j.bbrc.2024.149525.","DOI":"10.1016\/j.bbrc.2024.149525"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_064","doi-asserted-by":"crossref","unstructured":"Tsaryk, R., Yucel, N., Leonard, E.V., Diaz, N., Bondareva, O., Odenthal-Schnittler, M., Arany, Z., Vaquerizas, J.M., Schnittler, H., and Siekmann, A.F. (2022). Shear stress switches the association of endothelial enhancers from ETV\/ETS to KLF transcription factor binding sites. Sci. Rep. 12: 4795, https:\/\/doi.org\/10.1038\/s41598-022-08645-8.","DOI":"10.1038\/s41598-022-08645-8"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_065","doi-asserted-by":"crossref","unstructured":"Valentino, M., Dejana, E., and Malinverno, M. (2021). The multifaceted PDCD10\/CCM3 gene. Genes Dis 8: 798\u2013813, https:\/\/doi.org\/10.1016\/j.gendis.2020.12.008.","DOI":"10.1016\/j.gendis.2020.12.008"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_066","doi-asserted-by":"crossref","unstructured":"Valentino, M., Malinverno, M., Maderna, C., Pham, V.-C., R\u00f6del, C.J., Zanardi, F., Arce, M., Drufuca, L., Rossetti, G., Magnusson, P.U., et al.. (2024). BMI1 inhibition improves lesion burden in cerebral cavernous malformations. Circulation 150: 738\u2013741, https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.123.067438.","DOI":"10.1161\/CIRCULATIONAHA.123.067438"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_067","doi-asserted-by":"crossref","unstructured":"Vannier, D.R., Shapeti, A., Chuffart, F., Planus, E., Manet, S., Rivier, P., Destaing, O., Albiges-Rizo, C., Van Oosterwyck, H., and Faurobert, E. (2021). CCM2-deficient endothelial cells undergo a ROCK-dependent reprogramming into senescence-associated secretory phenotype. Angiogenesis 24: 843\u2013860, https:\/\/doi.org\/10.1007\/s10456-021-09809-2.","DOI":"10.1007\/s10456-021-09809-2"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_068","doi-asserted-by":"crossref","unstructured":"Voss, K., Stahl, S., Schleider, E., Ullrich, S., Nickel, J., Mueller, T.D., and Felbor, U. (2007). CCM3 interacts with CCM2, indicating common pathogenesis for cerebral cavernous malformations. Neurogenetics 8: 249\u2013256, https:\/\/doi.org\/10.1007\/s10048-007-0098-9.","DOI":"10.1007\/s10048-007-0098-9"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_069","doi-asserted-by":"crossref","unstructured":"Weng, J., Yang, Y., Song, D., Huo, R., Li, H., Chen, Y., Nam, Y., Zhou, Q., Jiao, Y., Fu, W., et al.. (2021). Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation. Am. J.\u00a0Hum. Genet. 108: 942\u2013950, https:\/\/doi.org\/10.1016\/j.ajhg.2021.04.005.","DOI":"10.1016\/j.ajhg.2021.04.005"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_070","doi-asserted-by":"crossref","unstructured":"Wu, W., Liu, Jun, Chen, Xiaoli, Zhu, P., Xu, J., Yue, J., Liu, X., Fang, J., Chen, Xiaohui, Pi, J., et al.. (2025). Shear stress-induced endothelial HEG1 signalling regulates vascular tone and blood pressure. Eur. Heart J.: ehaf742, https:\/\/doi.org\/10.1093\/eurheartj\/ehaf742.","DOI":"10.1093\/eurheartj\/ehaf742"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_071","doi-asserted-by":"crossref","unstructured":"W\u00fcstehube, J., Bartol, A., Liebler, S.S., Br\u00fctsch, R., Zhu, Y., Felbor, U., Sure, U., Augustin, H.G., and Fischer, A. (2010). Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc. Natl. Acad. Sci. USA 107: 12640\u201312645, https:\/\/doi.org\/10.1073\/pnas.1000132107.","DOI":"10.1073\/pnas.1000132107"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_072","doi-asserted-by":"crossref","unstructured":"Yin, J., Maggi, L., Wiesner, C., Affolter, M., and Belting, H.-G. (2024a). Oscillatory contractile forces refine endothelial cell-cell interactions for continuous lumen formation governed by Heg1\/Ccm1. Angiogenesis 27: 845\u2013860, https:\/\/doi.org\/10.1007\/s10456-024-09945-5.","DOI":"10.1007\/s10456-024-09945-5"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_073","doi-asserted-by":"crossref","unstructured":"Yin, J., Schellinx, N., Maggi, L., Gundel, K., Wiesner, C., Kotini, M.P., Lee, M., Phng, L.-K., Belting, H.-G., and Affolter, M. (2024b). Initiation of lumen formation from junctions via differential actomyosin contractility regulated by dynamic recruitment of Rasip1. Nat. Commun. 15: 9714, https:\/\/doi.org\/10.1038\/s41467-024-54143-y.","DOI":"10.1038\/s41467-024-54143-y"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_074","doi-asserted-by":"crossref","unstructured":"Zawistowski, J.S., Stalheim, L., Uhlik, M.T., Abell, A.N., Ancrile, B.B., Johnson, G.L., and Marchuk, D.A. (2005). CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum. Mol. Genet. 14: 2521\u20132531, https:\/\/doi.org\/10.1093\/hmg\/ddi256.","DOI":"10.1093\/hmg\/ddi256"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_075","doi-asserted-by":"crossref","unstructured":"Zhang, J., Clatterbuck, R.E., Rigamonti, D., Chang, D.D., and Dietz, H.C. (2001). Interaction between krit1 and icap1\u03b1 infers perturbation of integrin \u03b21-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation. Hum. Mol. Genet. 10: 2953\u20132960, https:\/\/doi.org\/10.1093\/hmg\/10.25.2953.","DOI":"10.1093\/hmg\/10.25.2953"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_076","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Deng, J., Sun, W., and Wang, Z. (2025). Cerebral cavernous malformation: from genetics to pharmacotherapy. Brain Behav. 15: e70223, https:\/\/doi.org\/10.1002\/brb3.70223.","DOI":"10.1002\/brb3.70223"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_077","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Jiang, F., Zeng, L., Wang, X., and Tu, S. (2018). PHACTR1 regulates oxidative stress and inflammation to coronary artery endothelial cells via interaction with NF-\u03baB\/p65. Atherosclerosis 278: 180\u2013189, https:\/\/doi.org\/10.1016\/j.atherosclerosis.2018.08.041.","DOI":"10.1016\/j.atherosclerosis.2018.08.041"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_078","doi-asserted-by":"crossref","unstructured":"Zhou, Z., Rawnsley, D.R., Goddard, L.M., Pan, W., Cao, X.-J., Jakus, Z., Zheng, H., Yang, J., Arthur, J.S.C., Whitehead, K.J., et al.. (2015). The cerebral cavernous malformation pathway controls cardiac development via regulation of endocardial MEKK3 signaling and KLF expression. Dev. Cell 32: 168\u2013180, https:\/\/doi.org\/10.1016\/j.devcel.2014.12.009.","DOI":"10.1016\/j.devcel.2014.12.009"},{"key":"2026080805591994593_j_hsz-2025-0246_ref_079","doi-asserted-by":"crossref","unstructured":"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). Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2\/4 signalling. 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