In this presentation Prof. Kastelein shows some data on the effects of recombinant human CRP infusion into healthy human volunteers. In vitro and in vivo effects of CRP suggest that more than being a predictor of future cardiovascular risk, it is also a mediator of disease (1-5). Is CRP directly causal in atherogenesis in humans, and if so what is the mechanism?

Prof. Kastelein presents the results of a study of recombinant human CRP infusion into healthy male human subjects, in terms of endothelial activation, cytokine release, and activation of inflammation and coagulation. These data demonstrate pro-atherogenic effects of CRP in an acute setting, after a single bolus at pathophysiological concentrations (6). These effects of CRP infusion suggest that if a plaque ruptures against a background of elevated CRP levels, it would be easier for a larger thrombus to form, leading to a more severe event.

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After viewing this presentation the participant will be able to discuss:

- Pro-atherogenic effects of CRP – in vitro and mouse studies
- Pro-atherogenic effects of recombinant human CRP infusion into healthy male human subjects

1. Subodh Verma, MD, PhD; Chao-Hung Wang, MD; Shu-Hong Li, MSc; Aaron S. Dumont, MD; Paul W.M. Fedak, MD; Mitesh V. Badiwala, BSc; Bikramjit Dhillon, BSc; Richard D. Weisel, MD; Ren-Ke Li, MD, PhD; Donald A.G. Mickle, MD; Duncan J. Stewart, MD. A Self-Fulfilling Prophecy: C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis Circulation. 2002;106:913.

2. Vincenzo Pasceri, MD, PhD; Jed Chang, BS; James T. Willerson, MD; Edward T. H. Yeh, MDModulation of C-Reactive Protein–Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti-Atherosclerosis Drugs Circulation. 2001;103:2531.

3. Ballou SP, Lozanski G.Induction of inflammatory ytokine release from cultured human monocytes by C-reactive protein. Cytokine. 1992 Sep;4(5):361-8.

4. Sridevi Devaraj, PhD; Dan Yan Xu, MD, PhD; Ishwarlal Jialal, MD, PhDC-Reactive Protein Increases Plasminogen Activator Inhibitor-1 Expression and Activity in Human Aortic Endothelial Cells: Implications for the Metabolic Syndrome and Atherothrombosis
Circulation. 2003;107:398.

5. Antoni Paul, PhD; Kerry W.S. Ko, PhD; Lan Li, MD; Vijay Yechoor, MD; Mark A. McCrory, BS; Alexander J. Szalai, PhD; Lawrence Chan, MBBS, DScC-Reactive Protein Accelerates the Progression of Atherosclerosis in Apolipoprotein E–Deficient Mice Circulation. 2004;109:647-655.

6. Radjesh J. Bisoendial, John J.P. Kastelein, Johannes H.M. Levels, Jaap J. Zwaginga, Bas van den Bogaard, Pieter H. Reitsma, Joost C.M. Meijers, Daniel Hartman, Marcel Levi, Erik S.G. Stroes Activation of Inflammation and Coagulation After Infusion of C-Reactive Protein in Humans Circulation Research. 2005;96:714.