TGFB1 and cerebral cavernous malformation: In both familial and sporadic CCM patients, TGF-β signaling is activated during pathological progression, as indicated by nuclear accumulation of endothelial pSMAD3 accompanied by expression of EndMT markers in lesions of familial and sporadic cavernomas (Maddaluno et al., 2013; Bravi et al., 2016).