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 (apoA₁-rich HDL). In this study we tested whether apoA₁ deficiency would adversely affect apoSAA concentration and lipid distribution in mouse plasma lipoproteins. Acute phase response (APR) was induced in C57BL/6J (apoA₁^+/+) and apoA₁-knockout mice (apoA₁^−/−) by a subcutaneous injection of silver nitrate. The APR increased cholesterol concentrations in LDL of apoA₁^−/− mice and apoA₁^+/+ mice in a like manner. In contrast to apoA₁^+/+ 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 apoA₁^−/− 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 apoA₁^−/− mice, HDL_L and HDL_H contained more apoSAA than in apoA₁^+/+ mice. These results indicate that apoA₁^−/− mice are not deterred from mounting an apoSAA response similar to apoA₁^+/+ mice and that apoA₁-rich HDL particles are not necessary for apoSAA transport in the plasma.