The mechanisms through which HDL promotes the proliferation of vascular endothelial cells will be analyzed. The physical process of binding, internalization, and degradation of HDL and HDL subclasses will be studied in conjunction with regulatory responses in the rate of cell proliferation and the cholesterol biosynthetic pathway. We will focus upon the cause and effect relationship between the effects of HDL and HDL subclasses upon cell proliferation and the modulation of HMG CoA reductase activity. As a specific metabolic response, HMG CoA reductase activity will be measured and considered as a reflection of substrate flux into sterols and non-sterol metabolites. The role of various subclasses of HDL in regulating the proliferation of HMG CoA reductase activity of vascular endothelial cells will be analyzed. Increases in enzyme activity will suggest increased rates of synthesis of sterols and/or non-sterol products from mevalonate. These alternatives will be investigated, as will their relationship to the cells' proliferative responses to the lipoproteins. We will also study which components of HDL are necessary in order for it to exert its mitogenic activity, which may occur through more than one mechanism. To this end, the lipid and apoprotein moieties of HDL will be tested and compared for mitogenic activity and metabolic effect on cholesterol efflux and HMG CoA reductase activity. Additionally, reconstituted HDL particles, constructed from various apoproteins and lipid moieties, will be studied.
| Neufeld, G; Gospodarowicz, D (1987) Protamine sulfate inhibits mitogenic activities of the extracellular matrix and fibroblast growth factor, but potentiates that of epidermal growth factor. J Cell Physiol 132:287-94 |
| Gospodarowicz, D; Massoglia, S; Cheng, J et al. (1986) Effect of retina-derived basic and acidic fibroblast growth factor and lipoproteins on the proliferation of retina-derived capillary endothelial cells. Exp Eye Res 43:459-76 |
| Neufeld, G; Massoglia, S; Gospodarowicz, D (1986) Effect of lipoproteins and growth factors on the proliferation of BHK-21 cells in serum free culture. Regul Pept 13:293-305 |
