Pressure and endothelial coculture upregulate myocytic Fas–FasL pathway and induce apoptosis by way of direct and paracrine mechanisms

Background Pressurized endothelial cell (EC)–smooth muscle cell (SMCs) coculture significantly increases the apoptosis of SMCs. Our current hypothesis was that in EC–SMC coculture, pressure upregulates SMC apoptosis SMCs through EC-derived paracrine factors and that SMC apoptosis is induced through Fas–Fas ligand (FasL) activation. Methods Conditioned media (CM) from ECs and SMCs exposed to ambient or high pressure was transferred to recipient SMCs. SMCs were stained with terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling. Fas and FasL expression was assessed in SMC grown in monoculture, coculture with EC, pressurized monoculture, and pressurized coculture with EC. Results CM from pressurized ECs caused a 30% increase in SMC apoptosis compared with CM from control ECs (P <.05). Pressure increased Fas and FasL expression in monocultured and cocultured SMCs (1.6-fold and 2.3-fold for Fas [P <.05] and 1.65-fold and 1.7-fold for FasL [P ≤.05]). Coculture had synergistic effect on Fas expression and no effect on FasL expression. Conclusions Pressure plays significant role in EC–SMC interaction, SMC apoptosis, and vascular remodeling.