Apolipoprotein D in Lipid Metabolism and Its Functional Implication in Atherosclerosis and Aging

Perdomo, German; Dong, H. Henry

Circulating ApoD is present mainly in HDL and to a lesser extent in LDL and VLDL [42, 43] (Fig. 3) . Nonetheless, little is known about the role of apoD in lipoprotein metabolism and its impact on atherosclerosis. Plasma apoD levels are significantly reduced in patients with Tangier disease, a rare autosomal recessive disorder that is caused by mutations in the ATP-binding cassette A1 (ABCA1) gene [34, 44] . As ABCA1 plays a key role in effluxing cholesterol from cells, ABCA1 loss-of-function results in diminished cholesterol removal from peripheral tissues, contributing to excessive accumulation of cholesterol in the body and increased risk of developing atherosclerosis in patients with Tangier disease [45] [46] [47] [48] [49] [50] . Recently, Vaisar et al. [51] took a proteomics approach to profile protein composition of HDL particles isolated from human subjects. Their studies reveal that HDL isolated from healthy individuals versus subjects with established CAD carry different protein cargos. Interestingly, apoD is highly enriched in HDL isolated from seven subjects with CAD, in comparison to six healthy controls. This observation seems paradoxical, as CAD patients are associated with lower HDL levels and apoD is mainly bound to HDL in the circulation. An increased apoD content in HDL may present a pathological marker or constitute a compensatory response to impaired cholesterol metabolism in subjects with established CAD.