Aspirin reduces the prothrombotic activity of C-reactive protein

E. Grad, M. Golomb, N. Koroukhov, J. A. Lawson, C. Lotan, G. A. Fitzgerald, Haim D. Danenberg

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Aim: C-reactive protein (CRP) is a risk marker and a potential modulator of vascular disease. Previous studies support a prothrombotic activity of CRP, with impaired thromboregulation. The present study examined the antithrombotic effect of aspirin in mice transgenic for human CRP (CRPtg mice). Mechanistic investigations further elucidated the effect of CRP on prostanoid metabolism in vivo and in vitro. Methods and Results: Administration of aspirin (30 mg kg-1 day-1) to CRPtg mice slowed the accelerated thrombosis after photochemical injury to the carotid (99 ± 32 vs. 45 ± 24 min and 75 ± 23 vs. 82 ± 26 min in wild-type mice vs. CRPtg mice, without and following aspirin treatment, respectively). Vascular injury modulated the expression of key pathways in prostanoid metabolism differently in CRPtg mice and wild-type mice. Suppression of cyclo-oxygenase2 (COX-2)-derived metabolism with suppression of prostaglandin. I2 (PGI2) synthase and PGI2 metabolism was recorded in the injured artery with increased thromboxane receptor expression. Aspirin therapy reduced the difference in PGI2 biosynthesis between CRPtg mice and wild-type mice. In vitro studies in human-derived cells further supported these findings. Incubation of human umbilical vein endothelial cells (HUVECs) with human recombinant CRP (5 μg mL-1) suppressed PGI2 synthase expression and significantly increased thromboxane receptor levels. Incubation of smooth muscle cells with CRP did not affect prostanoid expression. Conclusions: CRP modulates prostanoid metabolism to favor vascular occlusion. Elevated CRP levels might predispose to the cardiovascular hazard conferred by selective COX-2 inhibitors, and the risk mediated by CRP may be limited by aspirin.

Original languageEnglish
Pages (from-to)1393-1400
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Issue number8
StatePublished - Aug 2009
Externally publishedYes


  • Aspirin
  • C-reactive protein
  • Prostanoid
  • Vascular injury


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