Cholesterol enrichment enhances expression of sterol-carrier protein-2: implications for its function in intracellular cholesterol trafficking.

Overview

Cholesterol enrichment of vascular smooth muscle cells, as occurs under conditions of hypercholesterolemia and atherosclerosis, is accompanied by specific changes in cholesterol metabolism and in intracellular cholesterol trafficking. Sterol-carrier protein-2 (SCP2), an intracellular lipid binding protein, enhances the activation of enzymes involved in cholesterol metabolism. It may also enhance cholesterol efflux by regulating the size of the "fast" cholesterol pool available for efflux to high density lipoproteins. However, a definitive role for SCP2 in arterial cholesterol metabolism is unclear. Therefore, we examined the expression of SCP2 (13.1 kD), SCPx (58 kD), and p30 (30.8 kD) in cultured arterial smooth muscle cells under conditions of cholesterol enrichment. We found that SCP2, SCPx, and p30 are localized principally in the cytosolic fraction, with lesser amounts associated with the nuclear/peroxisomal fraction; the expression of SCP2 protein and mRNA, but not SCPx, is increased after exposure of smooth muscle cells to cationized LDL. In contrast to the increased expression of SCP2, the expression of p30 decreases after cholesterol enrichment of smooth muscle cells. Coupled with previous studies demonstrating enhanced cholesterol efflux from cholesterol-enriched smooth muscle cells in response to high density lipoproteins, our results suggest that increased expression of SCP2 may partly mediate the cholesterol trafficking process.