Effect of high and low density lipoproteins on proliferation of cultured bovine vascular endothelial cells.

Bovine vascular endothelial cells maintained on dishes coated with an extracellular matrix and exposedto medium supplemented with lipoprotein-deficient serum (LPDS) require the presence of lipoprotein to proliferate optimally. High density lipoprotein (HDL) seems to be the major factor involved in the proliferation of vascular endothelial cells. This is mostly due to its lack of toxicity when added at high concentration, as well as to its nondependence on LPDS to exhibit its mitogenic properties. Therefore, HDL at physiological concentrations (1,000--1,500 microgram protein/ml) can fully replace serum. Low density lipoprotein, unlike HDL, has a biphasic effect. Although mitogenic for vascular endothelial cells when added at low concentration, once physiological concentrations are reached it becomes toxic for the cells. Moreover, and in contrast with HDL, the mitogenic effect of low density lipoprotein was found to be a function of the LPDS concentration to which cultures were exposed. The substrate upon which cultures are maintained has been found to be an important factor if a mitogenic effect of HDL is to be observed. When maintained on plastic, cells proliferate poorly in response to HDL unless fibroblast growth factor is added to the medium. In contrast, when maintained on extracellular matrix, an optimal growth rate is induced by HDL, even in the absence of fibroblast growth factor. This suggests that, in vivo, the integrity of the basement membrane upon which endothelial cells rest and migrate is an important factor in determining the cells response to lipoproteins present in plasma.