Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity.

Abstract:

:Recent studies demonstrate that HDL's ability to promote cholesterol efflux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol efflux capacity during vascular disease are unclear. Inflammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol efflux capacity. We therefore tested the hypothesis that HDL's impaired efflux capacity is mediated by specific changes of its protein cargo. Humans with acute inflammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C efflux capacity was significantly impaired. Proteomic analyses demonstrated that HDL's cholesterol efflux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute inflammation caused a marked impairment of HDL-C efflux capacity that correlated with a large increase in HDL SAA. In striking contrast, the efflux capacity of mouse inflammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the inflammatory impairment of HDL-C efflux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo.

journal_name

J Lipid Res

authors

Vaisar T,Tang C,Babenko I,Hutchins P,Wimberger J,Suffredini AF,Heinecke JW

doi

10.1194/jlr.M059089

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

1519-30

issue

8

eissn

0022-2275

issn

1539-7262

pii

jlr.M059089

journal_volume

56

pub_type

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