KINETIC CHARACTERISTICS AND REGULATION OF HDL CHOLESTERYL ESTER AND APOLIPOPROTEIN TRANSPORT IN THE APOA-I- - MOUSE/

The concentration dependence and tissue distribution of high density l ipoprotein (HDL) cholesteryl ester and apolipoprotein (apo) transport were determined in apoA-I knockout mice (apoA-I-/-) that lack normal H DL in plasma, Rates of HDL cholesteryl ester clearance were highly sen sitive to plasma HDL cholesteryl ester concentrations with clearance r ates falling by 80% in the liver and by 95% in the adrenal glands when plasma HDL cholesteryl ester concentrations were acutely raised to le vels normally seen in control mice (similar to 50 mg/dl), With the exc eption of the brain, saturable HDL cholesteryl ester uptake was demons trated in all tissues of the body, with the adrenal glands and liver m anifesting the highest maximal transport rates (J(m)). The plasma conc entration of HDL cholesteryl ester necessary to achieve half-maximal t ransport (K-m) equaled 4 mg/dl in the adrenal glands and liver; as a c onsequence, HDL cholesteryl ester uptake by these organs is maximal (s aturated) at normal plasma HDL concentrations in the mouse. When expre ssed per whole organ, the liver was the most important site of HDL cho lesteryl ester clearance accounting for similar to 72% of total HDL ch olesteryl ester turnover at normal plasma HDL concentrations. HDL chol esteryl ester transporter activity and scavenger receptor type B1 (SR- BI) protein and mRNA levels were not up-regulated in any organ of apoA -I-/- mice even though these animals lack normal HDL.