title: ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans.
abstract: 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.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.i.vanleuven@amc.uva.nl
authors.forename: S I
authors.initials: SI
authors.lastname: van Leuven
authors.forename: R S
authors.initials: RS
authors.lastname: Birjmohun
authors.forename: R
authors.initials: R
authors.lastname: Franssen
authors.forename: R J
authors.initials: RJ
authors.lastname: Bisoendial
authors.forename: H
authors.initials: H
authors.lastname: de Kort
authors.forename: J H M
authors.initials: JH
authors.lastname: Levels
authors.forename: R L
authors.initials: RL
authors.lastname: Basser
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: J A
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: E S
authors.initials: ES
authors.lastname: Stroes
mesh_terms: 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*
chemical_list: D016632:Apolipoprotein A-I; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D002097:C-Reactive Protein