Glycosylation of HDL-Associated Proteins and Its Implications in Cardiovascular Disease Diagnosis, Metabolism and Function

Abstract

High-density lipoprotein (HDL) particles, long known for their critical role in the prevention of cardiovascular disease (CVD), were recently identified to carry a wide array of glycosylated proteins, and the importance of this glycosylation in the structure, function and metabolism of HDL are starting to emerge. Early studies have demonstrated differential glycosylation of HDL-associated proteins in various pathological states, which may be key to understanding their etiological role in these diseases and may be important for diagnostic development. Given the vast array and specificity of glycosylation pathways, the study of HDL-associated glycosylation has the potential to uncover novel mechanisms and biomarkers of CVD. To date, no large studies examining the relationships between HDL glycosylation profiles and cardiovascular outcomes have been performed. However, small pilot studies provide promising preliminary evidence that such a relationship may exist. In this review article we discuss the current state of the evidence on the glycosylation of HDL-associated proteins, the potential for HDL glycosylation profiling in CVD diagnostics, how glycosylation affects HDL function, and the potential for modifying the glycosylation of HDL-associated proteins to confer therapeutic value.

Keywords: APOC3; APOE; ApoA-I; N-glycosylation; O-glycosylation; glycosylation; high-density lipoprotein (HDL).

Figure 1

HDL particles are highly glycosylated, containing both glycoproteins that can be N- and O-glycosylated, and glycolipids, with glycan groups added enzymatically through highly regulated cellular processes. In contrast, non-enzymatic glycation of proteins such as ApoA-I can occur under conditions of hyperglycemia.