Uptake of endogenous cholesterol by a synthetic lipoprotein.
The addition of cholesterol-poor phospholipid liposomes to canine plasma in vivo and in vitro substantially alters the distribution of phospholipids, apoproteins, and, especially, cholesterol. In vivo, intravenously injected phospholipid liposomes remain discrete particles, which are readily distinguished from the normally occurring lipoproteins by their buoyant density and electrophoretic mobility. They acquire unesterified cholesterol from endogenous sources, thereby producing an acute rise in the concentration of this sterol in plasma. The liposomes also accumulate endogenous proteins, one of which is identified as apolipoprotein A-I. In vitro, phospholipid liposomes incubated with plasma acquire unesterified cholesterol and apolipoprotein A-I at the expense of high-density lipoproteins (HDL), the major carrier of cholesterol in normal canine plasma. In exchange, the HDL particles are enriched in phospholipids and become larger. At sufficiently high concentrations, the liposomes nearly completely deplete HDL of its unesterified cholesterol. Thus, there are generated two types of particles, both rich in apolipoprotein A-I and phospholipid, but one (modified HDL) containing mainly esterified cholesterol in its core and the other (modified liposomes) containing mainly unesterified cholesterol at its surface. It is concluded that phospholipid liposomes produce important changes in the distribution of lipids and protein in canine plasma, particularly at the expense of HDL. These changes appear to favor the mobilization of tissue cholesterol into the plasma, and may have application to atherosclerosis.
Williams
K J
KJ
Scanu
A M
AM
D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D002788:Cholesterol Esters / Q000097:blood; D004285:Dogs; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008081:Liposomes / Q000378:metabolism*; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D014461:Ultracentrifugation
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008081:Liposomes; D010743:Phospholipids; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase