[Modulations of proliferation between in vitro pulmonary artery endothelial cells and smooth muscle cells under...

Vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) are structurally and functionally closely connected. Their interactions may play important roles in the development of hypoxic pulmonary artery hypertension. In the present study, mitogenic regulations between cultured new bovine pulmonary arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells (PASMCs) under both normoxic and hypoxic conditions were investigated. Cell proliferation was assessed by 3H-thymidine incorporation and flow cytometry. Normoxic conditioned medium (CM) from cultured PASMCs inhibited 3H-thymidine incorporation of PAECs by 58% (P < 0.01), but normoxic or hypoxic CM from PAECs promoted or inhibited 3H-thymidine incorporation of PASM by 60% and 27% respectively (P < 0.01). When mixed PAECs and PASMCs were cultured for 24 h, relative 3H-thymidine incorporation of the mixed cells decreased by 22% (P < 0.01 vs monoculture) under normoxic condition, and increased by 75% or 44% under 0% O2 or 2.5% O2 (P < 0.01 vs normoxic mixculture). When PAECs and PASMCs were cocultured in either normoxic or hypoxic conditions, proliferation of PAECs was inhibited while that of PASMs was stimulated significantly (P < 0.01), as compared with that of homotypic cultured cells. These findings suggest that PAECs and PASMCs may mutually regulate their proliferation each other, and this mutual modulation may be changed under hypoxic condition.