(LB03-18-24) Extreme High Cholesterol Efflux Links to More Anti-inflammatory and Anti-oxidative Functions of HDL Than Extreme Low Cholesterol Efflux

Objectives: Reverse cholesterol transport (RCT) is the main anti-atherosclerotic function of HDL, and cholesterol efflux capacity (CEC) is a critical first step of this function. Inflammation and oxidation are metabolically linked to CEC, but the relationships between these functions have not been well characterized. The objective of this study is to determine if extreme high or low cholesterol efflux leads to differences in inflammation and anti-oxidative functions. We hypothesized that HDL's anti-inflammatory and antioxidative functions are associated with those with extremely high vs. low CEC. CEC was previously measured in 3000 participants in the Dallas Heart Study. Those below the 10th and above the 90th percentile were recruited 15-17 years later (n=36).

Methods: Frozen plasma was subjected to fast protein liquid chromatography (FPLC) using 3 tandem Superdex 200 columns. Total HDL and HDL subclasses (small, medium, and large) were isolated from plasma. We performed an anti-inflammatory capacity assay of HDL using human umbilical vein endothelial cells (HUVEC).

Results: CEC elucidated significant differences in patterns between high and low-efflux groups, p=0.05. Paraoxonase 1 (PON1) levels were significantly increased in plasma samples of the high vs. low CEC group. The high CEC group showed significantly increased HDL anti-inflammatory capacity compared to the low CEC group, p=0.05. THP1 monocytes treated with HDL showed significantly decreased CD40 and serum amyloid A (SAA), myeloperoxidase (MPO), and tumor necrosis factor α (TNF-α) levels in the high CEC compared to the low CEC groups, p=0.05.

Conclusions: In conclusion, these findings suggest that a key measure of RCT is strongly related to HDL's anti-inflammatory and antioxidative functions. Future studies are warranted to determine the complementary information these metabolic markers contribute to cardiovascular risk.

Funding Sources: NIH/NHLBI R01HL136724 and NIH/NHLBI K24HL146838