Another consistently upregulated gene in EC cluster 9 was KLF2, highlighting the pivotal role of augmented MEKK3-KLF2/4 signaling in CCM disease that leads to profound endothelial dysfunction and aberrant angiogenesis via, for example, increased Rho/ROCK and PI3K-mTOR signaling or endothelial-to-mesenchymal transition (EndMT) [17, 66, 68, 82]. This evidence concerns the gene MTOR and cerebral cavernous malformation.