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

Perdomo, German; Dong, H. Henry

ApoD is categorized as apolipoprotein due to its initial isolation from human HDL. Indeed, circulating apoD is bound mainly to HDL, correlating with the ability of apoD to associate via covalent cross-link with apoA-II. Plasma apoD is also present at a relatively low content in VLDL and LDL, suggesting that apoD plays significant roles in both triglyceride and cholesterol metabolism. Consistent with this notion, apoD polymorphism is associated with lipid disorders, as characterized by elevated plasma triglyceride levels and/or reduced HDL levels. ApoD is enriched in HDL isolated from patients with established CAD. Likewise, increased apoD deposition is detected in the atherosclerotic plaques of both human and rodent origins. However, a cause and effect relationship between aberrant apoD production and abnormal lipoprotein metabolism remains unknown. For example, how do apoD mutations result in elevated plasma triglyceride levels? Does apoD affect hepatic VLDL production and plasma VLDL clearance? Does apoD protect against or contribute to the pathogenesis of atherosclerosis? While apoD is present in HDL in dimerization with apoA-II, it is not clear how this intermolecular cross-link affects HDL remodeling and impacts cholesterol metabolism. Obviously, further studies are needed to characterize the role of apoD in Figure 5 . ApoD is localized to atherosclerotic plaques of apoE-deficient mice. Proximal aorta sections of male apoE knockout mice were subjected to oil red O staining (A), and to immunohistochemistry using control rabbit IgG against bacterial β-galactosidase (B) and rabbit anti-apoD antibody (C). The secondary antibody used in immunostaining is the donkey antirabbit IgG conjugated with Cy3. ApoD was stained red in the atherosclerotic plaque (C), as indicated by arrow. Elastic fibers of vessels were auto-fluorescent blue, as indicated by arrowhead. Bar = 50 µm. www.impactaging.com triglyceride and cholesterol metabolism and decipher the underlying mechanism that links apoD dysregulation to abnormalities in lipoprotein metabolism, accounting for heightened risk of developing CAD in subjects with obesity and/or diabetes.