Inflammation modulates human HDL composition and function in vivo

Objectives: Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans. Methods and results: We employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-related parameters in vivo. Endotoxemia induced remodelling of HDL with depletion of pre-beta 1a HDL particles determined by 2-D gel electrophoresis (-32.2 +/- 9.3% at 24 h, p < 0.05) as well as small (23.0 +/- 5.1%, p < 0.01, at 24 h) and medium (57.6 +/- 8.0% at 16 h, p < 0.001) HDL estimated by nuclear magnetic resonance (NMR). This was associated with induction of class II secretory phospholipase A2 (similar to 36 fold increase) and suppression of lecithin: cholesterol acyltransferase activity (-20.8 +/- 3.4% at 24 h, p < 0.01) and cholesterol ester transfer protein mass (-22.2 +/- 6.8% at 24 h, p < 0.001). The HDL fraction, isolated following endotoxemia, had reduced capacity to efflux cholesterol in vitro from SR-BI and ABCA1, but not ABCG1 transporter cell models. Conclusions: These data support the concept that atherogenic-HDL dysfunction and impaired RCT occur in human inflammatory syndromes, largely independent of changes in plasma HDL-C and ApoA-I levels. (C) 2012 Elsevier Ireland Ltd. All rights reserved.