Intravenous apoA-I/lecithin discs increase pre-beta-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans

The extent to which plasma HDL concentration regulates reverse cholesterol transport (RCT) is not known. The principal acceptors of unesterified chole sterol (UC from cultured cells are small pre-beta -HDL, which we have shown increase in plasma during intravenous infusion of apolipoprotein A-I/phosp hatidylcholine (apoA-I/PC) discs in humans. We have now examined the effect s on tissue fluid HDL and RCT. ApoA-I/PC or proapoA-I/PC discs were infused into 16 healthy males. Eleven had been given intravenous radiocholesterol to label tissue pools; in 12 prenodal leg lymph was collected throughout; a nd in 8 all feces were collected. The rise in small pre-beta -HDL in plasma was associated with increases in 1) pre-beta -HDL concentration in lymph ( all subjects), 2) the size of other lymph HDL (four of four subjects), 3) t he cholesterol content of lymph lipoproteins relative to plasma lipoprotein s (P < 0.01, n = 4), 4) cholesterol-specific radioactivity in lymph (five o f nine subjects), 5) plasma lathosterol (P < 0.004, n = 4), 6) plasma chole sterol esterification rate (P < 0.001, n = 4), and 7) fecal bile acid excre tion (P < 0.001, n = 8).jlr These results support the hypothesis that small pre-beta -HDL generated in plasma readily cross endothelium into tissue fl uid, and thereby promote efflux of UC from peripheral cells. After delivery to the liver, peripheral cholesterol appears to be utilized more for bile acid synthesis than for biliary cholesterol secretion in humans.