Serum albumin is a significant intermediate in cholesterol transfer between cells and lipoproteins

The function of albumin in the movement of cholesterol into and out of non-cholesterol-loaded fibroblasts has been investigated, Cholesterol efflux from cholesterol-labeled normal human skin fibroblasts to fatty acid-free human serum albumin (HSA) is biphasic with a rapid first phase that plateaus at about 15 min followed by a nearly linear phase up to 90 min, the longest incubation in this study. Saturation of efflux is observed at about 10 mg of albumin/mL. Efflux is specific to albumin since other molecules, such as ovalbumin or gelatin, do not induce efflux. The ability of PISA to induce cellular cholesterol efflux is low compared to reconstituted discoidal lipoprotein A-I (LpA-I), PISA at 2 mg/mL produces a rate of cholesterol efflux similar to that of LpA-I at 45 mu g of protein/mL; however, these concentrations are within the physiological range for both HSA and apolipoprotein A-I (apoA-I). The efflux to the medium containing both LpA-I and HSA is greater than that to each of them alone but does not show complete additivity, indicating a competition between HSA and LpA-I. The HSA-mediated cholesterol movement is bidirectional as demonstrated by the transfer of cholesterol from HSA-(H-3)-cholesterol complexes to fibroblasts; moreover, the HSA-mediated transfer is much faster than that from cholesterol-containing LpA-I (0.8 versus 0.2 pmol (mu g of cell protein)(-1) (90 min)(-1). However, the presence of either low-density lipoprotein (LDL) or LpA-I in the incubation medium significantly inhibits the transfer of cholesterol from HSA-(H-3)-cholesterol complexes to fibroblasts, thus allowing the bidirectional transfer of cholesterol between HSA and cells to possibly operate as a net efflux, In conclusion, albumin plays a significant role in cholesterol transfer between cells and lipoproteins.