Studies of human tissues demonstrated that not only both Klf4 and pSmad 3 were upregulated in the endothelium lining human familial and sporadic CCM malformations, but that this was accompanied by a substantial upregulation of EndMT markers such as S100a4, αSMA, fibronectin, N-cadherin and ID1. This evidence concerns the gene KLF4 and cerebral cavernous malformation.