High-density lipoproteins neutralize C-reactive protein proinflammatory activity.

Abstract:

BACKGROUND:C-reactive protein (CRP), a well-recognized marker of atherosclerosis, has recently been suggested to have a direct proinflammatory effect. The constitutive expression of low levels of CRP in normal plasma suggests the likelihood that a natural factor exists to neutralize the effect of CRP. This factor(s) has not yet been identified. Method and Results- The proinflammatory effect of CRP was measured by the induction of inflammatory adhesion molecules in human umbilical vein endothelial cells (HUVECs). We show that CRP significantly induced upregulation of adhesion molecules in both protein and mRNA levels. The CRP-induced expression of these inflammatory adhesion molecules was completely suppressed when the cells were preincubated with a physiological concentration (1 mg/mL apolipoprotein A-I) of HDLs derived from human plasma (native HDL) or reconstituted HDL (rHDL) at a very low concentration (0.01 mg/mL apolipoprotein A-I). A novel mechanism of HDL inhibition is likely to operate, because (1) rHDL was 100 times more potent than native HDL, (2) preincubation with HDL and its sustained presence were obligatory, and (3) oxidized 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine was the fundamental active component. CONCLUSIONS:The CRP-induced upregulation of inflammatory adhesion molecules in HUVECs was completely prevented by HDL via their oxidized phospholipid components.

journal_name

Circulation

journal_title

Circulation

authors

Wadham C,Albanese N,Roberts J,Wang L,Bagley CJ,Gamble JR,Rye KA,Barter PJ,Vadas MA,Xia P

doi

10.1161/01.CIR.0000127419.45975.26

subject

Has Abstract

pub_date

2004-05-04 00:00:00

pages

2116-22

issue

17

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000127419.45975.26

journal_volume

109

pub_type

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