ApoAI-phosphatidylcholine infusion neutralizes the atherothrombotic effects of C-reactive protein in humans

作者：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

来源：Journal of Thrombosis and Haemostasis, 2009, 7(2): 347-354.

DOI：10.1111/j.1538-7836.2008.03175.x

• atherothrombosis
• C-reactive protein
• endothelium
• high-density lipoprotein
• inflammation

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.

• 出版日期2009-2