Abstract 64: HDL Glycosylation is Associated with HDL’s Anti-Inflammatory Function and is Responsive to Dietary Intervention

Although HDL cholesterol (HDL-C) levels are protective against cardiovascular disease (CVD) risk, raising HDL-C pharmaceutically has not led to improvements in cardiovascular outcomes. It is becoming clear that HDL composition and function are more important than HDL concentrations in determining risk. This study set out to determine whether glycosylation differences in HDL-associated glycoproteins affect HDL’s anti-inflammatory function. HDL were purified from healthy subjects (n=10), who consumed in randomized order a fast food (FF) diet and a Mediterranean (Med) diet for 4 days, with a 4-day washout between arms. All foods were provided in this isocaloric cross-over intervention trial, which was approved by the UC Davis IRB. Concentrations of HDL-bound serum amyloid A (SAA), apolipoprotein A-I (ApoA-I), apolipoprotein C-III (ApoC-III), α-1-antitrypsin (A1AT), and α-2-HS-glycoprotein (A2HSG); and the site-specific glycosylation of ApoC-III, A1AT, and A2HSG were measured. Secretion of TNF-α in stimulated monocytes was measured to assess HDL anti-inflammatory function. HDL glycosylation was altered by the dietary interventions and correlated with changes in the amount of TNF-α secreted by stimulated monocytes. HDL glycosylation profiles were different in response to the FF diet vs. the Med diet. HDL with a diminished capacity to suppress TNF-α secretion were enriched in ApoC-III and desialylated A2HSG, depleted in A1AT, and had lower levels of sialylation across glycoproteins. Our results demonstrate that HDL glycoprotein composition, including site-specific glycosylation, is responsive to dietary intervention and correlates with HDL’s ability to modulate TNF-α response in stimulated monocytes. These data suggest that the measurement of HDL glycosylation profiles may be useful in stratifying CVD risk and detecting individuals with impaired HDL anti-inflammatory function.