The acute phase response in apolipoprotein A-1 knockout mice: apolipoprotein serum amyloid A and lipid distribution in plasma high density lipoproteins

Abstract

In plasma, the bulk of apoSAA, a positive acute phase reactant protein, is transported in high density lipoproteins (HDL), especially HDL H (apoA 1-rich HDL). In this study we tested whether apoA 1 deficiency would adversely affect apoSAA concentration and lipid distribution in mouse plasma lipoproteins. Acute phase response (APR) was induced in C57BL/6J (apoA 1 +/+) and apoA 1-knockout mice (apoA 1 −/−) by a subcutaneous injection of silver nitrate. The APR increased cholesterol concentrations in LDL of apoA 1 −/− mice and apoA 1 +/+ mice in a like manner. In contrast to apoA 1 +/+ mice, concentrations of cholesterol, phospholipids and proteins in both HDL L (1.063< d<1.103 g/ml) and HDL H (1.103< d<1.21 g/ml) were significantly increased by the APR in apoA 1 −/− mice. Total concentration of plasma apoSAA and its distribution in lipoprotein fractions was similar in both APR groups. The bulk of plasma apoSAA was contained in HDL and not in VLDL or LDL even when the HDL concentration was low. In apoA 1 −/− mice, HDL L and HDL H contained more apoSAA than in apoA 1 +/+ mice. These results indicate that apoA 1 −/− mice are not deterred from mounting an apoSAA response similar to apoA 1 +/+ mice and that apoA 1-rich HDL particles are not necessary for apoSAA transport in the plasma.