REGULATION OF CHOLESTEROL IN VASCULAR ENDOTHELIUM

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The effect and mechanisms through which lipoproteins regulate MVA metabolism and act as competence factors for cultured cells will be analyzed using as models normal diploid cells (capillary endothelial cells (CE), vascular smooth muscle cells) and an established cell line (MDCK cells). The ability of very low density lipoproteins (VLDL) which are LDL precursors to support cell shape and proliferation will be determined using cultures exposed or not to compactin. Their effects will be compared to that of HDL. As a specific VLDL and HDL metabolic response, their effect on HMG-CoA reductase will be measured and considered as a reflection of substrate flux into sterols and nonsterol metabolites. We will determine which key nonsterol products resulting from MVA metabolism would be relevant to the control of cell proliferation and cell shape and would explain the ability of lipoproteins to act as competence factors. Our attention will be focused on the synthesis of terpenes which modify specific polypeptides post translationally. The effect of HDL, VLDL and isolated components (phospholipid liposomes, apolipoproteins) on terpene synthesis and their incorporation into polypeptides as well as the effect of b FGF ( a progression factor for CE cells) on such a process will be examined using as models sparse CE cells exposed or not to compactin.