Influence of macrophage-derived apolipoprotein E on plasma lipoprotein distribution of apolipoprotein A-I in apolipoprotein E-deficient mice.

High density lipoprotein (HDL) cholesterol in apolipoprotein (apo) E-deficient mice is decreased. It has been suggested that apoA-I is lost from HDL in these mice because it must substitute for apoE as a structural protein for the abnormal cholesterol-rich lipoproteins. Therefore, we examined in vivo the influence of selective apoE expression on plasma HDL cholesterol in apoE-deficient mice. Bone marrow transplantation was used to establish macrophage-specific expression of apoE. Bone marrow transplantation normalized plasma triglycerides and significantly reduced total plasma cholesterol, but it did not increase hepatic apoA-I mRNA levels or total plasma apoA-I. Although total plasma apoA-I was not increased, HDL cholesterol measured following chromatographic separation was elevated twofold. Furthermore, plasma apoA-I was recovered from this HDL in animals expressing macrophage apoE. Compared to HDL of wildtype mice, this HDL had a similar chromatographic size distribution, but it lacked apoE and was more negatively charged. These studies indicated that plasma apoA-I distribution and HDL composition are influenced by apoE and that the abnormal apoA-I lipoprotein distribution of apoE-deficient mice can be altered in vivo by macrophage-derived apoE.