“…Although paracrine signaling and direct cell-cell contact between arterial ECs and SMCs have been shown in numerous studies to regulate the phenotype of SMCs (4,10,15,18,19,26,27,31,32,34), the signals exchanged during the direct cell-cell contact have not been fully defined. Using the EC/ SMC coculture system established by Isakson communication between the cocultured cells was blocked by pharmacological inhibitors or genetic ablation of the gap junctional protein Cx-43, the differentiation of PASMCs was prevented.…”