SUPERNATANT OF ENDOTHELIAL-CELLS EXPOSED TO LAMINAR-FLOW INHIBITS MESANGIAL CELL-PROLIFERATION

We investigated the effects of culture medium conditioned with endothe lial cells exposed to hemodynamic shear forces on modulation of mesang ial cell (MC) growth. Confluent monolayers of bovine aortic endothelia l cells, grown in medium containing 10% fetal calf serum, were exposed to static or to laminar flow conditions for 24 h using a cone-and-pla te device. Endothelial cell-conditioned medium was used to study the g rowth of bovine MC by [H-3]thymidine uptake. The proliferative respons e of MC to fresh medium (containing 10% fetal calf serum) and to cultu re medium from endothelial cells under static flow [66.7 +/- 34.1 vs. 73.9 +/- 30.0 counts/min (cpm) X 10(-3)] was comparable. In contrast, medium conditioned with endothelial cells exposed to laminar shear str ess of 8 dyn/CM2 almost completely abolished MC proliferation (5.8 +/- 6.9 cpm X 10(-3), P < 0.01). To establish whether this effect is due to endothelial cell production of a substance that inhibits MC prolife ration or simply to metabolization of serum growth factors in the cult ure medium, we performed shear stress experiments using serum free med ium and we added 10% fetal calf serum after shear exposure just before the proliferation assay. In this condition a significant antiprolifer ative effect of endothelial cell supernatant under laminar flow was ob tained (27.7 +/-23.4 vs. 68.8 +/- 45.8 cpm X 10(-3), laminar vs. stati c, P < 0.05), suggesting that endothelial cells under shear stress eff ectively produce a factor that inhibits MC proliferation. These result s would suggest that local glomerular capillary blood flow could play a role in the regulation of MC mitogenesis.