biostudies-literatureLi LNHLBI NIH HHSNINDS NIH HHSNIH HHS2906-2917https://www.ebi.ac.uk/biostudies/studies/S-EPMC10599232biostudies-literatureUnknown54(11)<h4>Background</h4>Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endothelial cells. Gain-of-function mutations in <i>PIK3CA</i> (encoding the enzymatic subunit of the PI3K (phosphoinositide 3-kinase) pathway associated with cell growth) synergize with CCM gene loss-of-function to generate rapidly growing lesions.<h4>Methods</h4>We recently developed a model of CCM formation that closely reproduces key events in human CCM formation through inducible CCM loss-of-function and <i>PIK3CA</i> gain-of-function in mature mice. In the present study, we use this model to test the ability of rapamycin, a cliniStrokemTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.PMC10599232R01 NS100949S10 OD016393R01 HL094326P01 NS092521Griffin JYang JMericko-Ishizuka PKahn MLAlcazar RMarchuk DARen AALi LMoore TBurkhardt JKAwad IAShenkar RLightle RBockman JGao SDeBiasse DSu YSfalsemTORC1 Inhibitor Rapamycin Inhibits Growth of Cerebral Cavernous Malformation in Adult Mice.<h4>Background</h4>Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endothelial cells. Gain-of-function mutations in <i>PIK3CA</i> (encoding the enzymatic subunit of the PI3K (phosphoinositide 3-kinase) pathway associated with cell growth) synergize with CCM gene loss-of-function to generate rapidly growing lesions.<h4>Methods</h4>We recently developed a model of CCM formation that closely reproduces key events in human CCM formation through inducible CCM loss-of-function and <i>PIK3CA</i> gain-of-function in mature mice. In the present study, we use this model to test the ability of rapamycin, a clini2023-01-01T00:00:00Z2023 Nov2026-06-03T07:19:50.978Z2025-04-06T09:32:38.732ZS-EPMC105992323774670510.1161/strokeaha.123.04410810.1161/STROKEAHA.123.044108