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ApoAI‐phosphatidylcholine infusion neutralizes the atherothrombotic effects of C‐reactive protein in humans
Author(s) -
VAN LEUVEN S. I.,
BIRJMOHUN R. S.,
FRANSSEN R.,
BISOENDIAL R. J.,
DE KORT H.,
LEVELS J. H. M.,
BASSER R. L.,
MEIJERS J. C. M.,
KUIVENHOVEN J. A.,
KASTELEIN J. J.,
STROES E. S.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03175.x
Subject(s) - inflammation , c reactive protein , phosphatidylcholine , recombinant dna , coagulation , chemistry , lipoprotein , pharmacology , medicine , in vitro , endocrinology , cholesterol , biochemistry , phospholipid , membrane , gene
Summary. 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. Conclusion: 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.