Current Understanding of Circulating Apolipoprotein E-Containing High-Density Lipoproteins and Their Clinical Utility in Cardiovascular Disease Risk Assessment

Plasma high-density lipoprotein (HDL) plays a key role in transporting accumulated excess cholesterol from the peripheral tissues to the liver, and has other multiple cardioprotective functions, including antioxidant, anti-inflammatory, and antithrombotic effects. However, HDL-cholesterol (HDL-C) levels, which are commonly measured in a clinical testing, may not necessarily reflect the beneficial aspects of HDLs. In fact, recent studies have shown that increasing HDL-C with medication does not reliably prevent cardiovascular disease. Furthermore, recent advances in proteomic technology have revealed hundreds of proteins associated with HDLs, which contribute to their structural heterogeneity and functional diversity. Accordingly, identifying specific HDL family members is useful in assessing cardiovascular disease risk, rather than evaluating HDL as a single family. Certain HDLs contain apolipoprotein E (apoE), which plays an important role in cholesterol transport. However, our understanding of apoE-containing HDL (apoE-HDL) has become complex as apoE-HDL is a heterogeneous population that differs in particle compositions and sizes, as well as biological functions. This review focuses on apoE-HDL and summarizes its characteristics and functions as well as the clinical significance of its measurement, discussing its potential as a novel biomarker for cardiovascular disease risk assessment.