Inflammation modulates human HDL composition and function in vivo.

ABSTRACT: Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans.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-?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 (~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.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.

SUBMITTER: de la Llera Moya M 

PROVIDER: S-EPMC3361641 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature