Interactions between cultured bovine arterial smooth muscle cells and endothelial cells; studies on the release of growth inhibiting and growth stimulating factors

The balance of growth stimulating and growth inhibiting factors in the arterial wall might be of importance in the pathogenesis of atherosclerosis. A method using different dialysis steps was used to allow the simultaneous study of micromolecular (dialysable) and macromolecular (non-dialysable) substances in conditioned media from bovine and human arterial endothelial cells and smooth muscle cells in culture. Micromolecular substances inhibited the proliferation of aortic smooth muscle cells and endothelial cells, while the macromolecular substances were growth stimulating. The effect of the micromolecular and macromolecular factors was dose dependent, but only the micromoleculars were affected by conditioning time. The micromoleculars were heat stable. The effect of macromoleculars was completely abolished by heating to 100 degrees C for 5 minutes. Confluent cells released relatively more growth inhibiting and less growth stimulating activity while the balance was changed in subconfluent cells showing an increased release of growth stimulating activity per cell. A co-culture model for endothelial and smooth muscle cells demonstrated that the confluent aortic endothelial cells released relatively more growth inhibiting activity. These models seem suitable for the study of interactions of growth inhibition and stimulation between arterial cells in vitro in the normal or pathological state.