ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans.
BACKGROUND
High-density lipoprotein (HDL) exerts a variety of anti-atherothrombotic functions, including a potent anti-inflammatory impact. In line, the direct pro-inflammatory effects of C-reactive protein (CRP) can be attenuated by HDL in vitro.


OBJECTIVE
To evaluate whether this also holds true in humans, we assessed the ability of reconstituted HDL to neutralize CRP-mediated activation of coagulation and inflammation.


METHODS
Fifteen healthy male volunteers received an infusion of recombinant human (rh)CRP (1.25 mg kg(-1) body weight). In eight of these volunteers, an infusion of human apoAI reconstituted with phosphatidylcholine (apoAI-PC; 80 mg kg(-1) body weight) preceded rhCRP infusion.


RESULTS
Infusion of rhCRP alone elicited an inflammatory response and thrombin generation. In individuals who received apoAI-PC prior to rhCRP, these effects were abolished. Parallel tests in primary human endothelial cells showed that apoAI-PC preincubation with rhCRP abolished the CRP-mediated activation of inflammation as assessed by IL-6 release. Although we were able to show that rhCRP co-eluted with HDL after size-exclusion chromatography, plasmon surface resonance indicated the absence of a direct interaction between HDL and CRP.


CONCLUSIONS
Infusion of apoAI-PC prior to rhCRP in humans completely prevents the direct atherothrombotic effects of rhCRP. These findings imply that administration of apoAI-PC may offer benefit in patients with increased CRP.
van Leuven
S I
SI
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.i.vanleuven@amc.uva.nl
Birjmohun
R S
RS
Franssen
R
R
Bisoendial
R J
RJ
de Kort
H
H
Levels
J H M
JH
Basser
R L
RL
Meijers
J C M
JC
Kuivenhoven
J A
JA
Kastelein
J J
JJ
Stroes
E S
ES
D000328:Adult; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000494:pharmacology*; D050197:Atherosclerosis; D002097:C-Reactive Protein / Q000008:administration & dosage / Q000494:pharmacology*; D042783:Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000008:administration & dosage; D011994:Recombinant Proteins; D013927:Thrombosis / Q000209:etiology*
D016632:Apolipoprotein A-I; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D002097:C-Reactive Protein