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 lipoprotein (HDL) cholesteryl ester and apolipoprotein (apo) transport were determined in apoA-I knockout mice (apoA-I-/-) that lack normal HDL in plasma. Rates of HDL cholesteryl ester clearance were highly sensitive to plasma HDL cholesteryl ester concentrations with clearance rates falling by 80% in the liver and by 95% in the adrenal glands when plasma HDL cholesteryl ester concentrations were acutely raised to levels normally seen in control mice (approximately 50 mg/dl). With the exception of the brain, saturable HDL cholesteryl ester uptake was demonstrated in all tissues of the body, with the adrenal glands and liver manifesting the highest maximal transport rates (Jm). The plasma concentration of HDL cholesteryl ester necessary to achieve half-maximal transport (Km) equaled 4 mg/dl in the adrenal glands and liver; as a consequence, HDL cholesteryl ester uptake by these organs is maximal (saturated) at normal plasma HDL concentrations in the mouse. When expressed per whole organ, the liver was the most important site of HDL cholesteryl ester clearance accounting for approximately 72% of total HDL cholesteryl ester turnover at normal plasma HDL concentrations. HDL cholesteryl 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.