Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall

Abstract

Apoprotein E (apoE) is synthesized by a number of tissues including the liver, brain, adipose tissue, and artery wall. The majority of apoE is found in the plasma associated with specific lipoprotein subclasses and is derived primarily from the liver. However the fact that apoE expression is sustained in nonhepatic tissues suggests that the local production must have some unique functional attribute. ApoE is involved in many steps in lipid and lipoprotein homeostasis, for the triglyceride-rich lipoproteins and for HDL. ApoE is also important for lipid homeostasis in the brain, artery wall, and adipose tissue through its synthesis by glial cells, adipocytes, and macrophages. In addition, nonlipid related functions have also been attributed to apoE, including effects on immune response and inflammation, oxidation, and smooth muscle proliferation and migration. Some of these effects have been shown to be dependent upon different domains of the protein, different concentrations, and lipidation state. Thus, this multifunctional protein impacts normal and pathophysiology at multiple levels.

Fig. 1.

Roles of Apolipoprotein E (apoE). ApoE synthesized by a number of tissues contributes to plasma levels, with the brain and endocrine cells contributing little if any to plasma apoE levels. Plasma-derived and endogenous apoE (curved arrow) may participate in the various functions of apoE in most of these tissues. CSF, cerebral spinal fluid.