Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I - Potential reverse cholesterol transport in humans

Backgronnd-Apolipoprotein (apo) A-I is the major protein component of HDL, a cholesterol transport particle that protects against atherosclerosis. Apo A-I is believed to promote reverse cholesterol transport, transferring cho lesterol from peripheral cells to the liver for subsequent elimination. To test this hypothesis in humans, we measured fecal steroid excretion before and after the intravenous infusion of human proapo A-I (precursor of apo A- I) liposome complexes. Methods and Results-Four subjects with heterozygous familial hypercholester olemia were studied under standardized conditions. The fecal excretion of b ile acids and neutral sterols was determined for 9 days before and 9 days a fter an intravenous infusion of recombinant human proapo A-I (4 g protein) liposome complexes. Plasma apoA-I and HDL cholesterol levels increased tran siently (mean peak concentrations were 64% and 35% above baseline, respecti vely) during the first 24 hours. Mean lipoprotein lipid and apolipoprotein levels were not different during the 2 collecting periods, however. Serum l athosterol, a precursor of cholesterol whose concentration reflects the rat e of cholesterol synthesis in vivo, was also unchanged. The fecal excretion of cholesterol (neutral sterols and bile acids) increased in all subjects (mean increase, +39% and +30%, respectively), corresponding to the removal of approximate to 500 mg/d excess cholesterol after infusion. Control infus ions with only liposomes in 2 of the patients did not influence lipoprotein pattern or cholesterol excretion. Conclusions-Infusion of proapoA-I liposomes in humans promotes net choleste rol excretion from the body, implying a stimulation of reverse cholesterol transport. This mechanism may prove useful in the treatment of atherosclero sis.