Rapamycin, but not propranolol, can partially revert CCM phenotype in brain endothelial cells and ameliorates chronic cavernoma development in combination with lapatinib

Brain microvascular endothelial cells (mBMEC) deficient in Ccm3 were used to model CCMs in vitro. Cells were treated with propranolol (10 µM) and rapamycin (100 nM) for various durations. RNAseq was employed to analyze gene expression. Propranolol did not significantly affect the CCM phenotype in mBMEC, failing to revert gene expression changes. Rapamycin partially reversed gene expression changes caused by Ccm3 deficiency, affecting genes such as Nos3, Adamts1, and Thbs1, known to be important for cavernoma pathogenesis in endothelial cells deficient for Ccm3. Propranolol's lack of efficacy in brain endothelial cells raises questions about its mechanism of action and potential benefits in CCM treatment.