Rabbit aortic endothelial cell hypoxia induces secretion of transforming growth factor beta and augments macrophage...

Hypoxic injury of vascular endothelial cells is hypothesized to be the initial cellular event in the formation of an atherosclerotic lesion. We studied the effect of various oxygen tensions on rabbit aortic endothelial cells in culture to determine macrophage adhesion and analyzed endothelial cell-conditioned media for fibroblast mitogenesis and transforming growth factor beta production. Fibroblast mitogenesis assay of endothelial cell-conditioned media revealed decreased activity at lower oxygen tensions. Further study revealed an inverse relationship between oxygen tension and aortic endothelial cell production of transforming growth factor beta despite lower total numbers of viable aortic endothelial cells at lower oxygen tensions. When rabbit aortic endothelial cells grown at various oxygen tensions were incubated with five day old bone marrow macrophages, an increase in macrophage adherence to aortic endothelial cells was noted at low oxygen tensions. Our observations suggest that aortic endothelial cell hypoxia leads to the production of transforming growth factor beta, a known monocyte chemoattractant. Monocytes may marginate and then adhere to endothelial cells, their adherence being augmented by endothelial cell hypoxia. This may contribute to the initial cellular events in the formation of an atherosclerotic lesion.