- 作者：Radjesh J. Bisoendial ; Rakesh S. Birjmohun ; Fatima Akdim ; Cornelis van ‘ ; t Veer ; C. Arnold Spek ; Daniel Hartman ; Els R. de Groot ; Danute M. Bankaitis-Davis ; John J.P. Kastelein ; Erik S.G. Stroes
- 关键词：Atherosclerosis ; Cardiovascular everts ; C-reactive protein ; Infection ; Leukocytes
- 刊名：The American Journal of Medicine
- 出版年：2009
- 出版时间：June 2009
- 年：2009
- 卷：122
- 期：6
- 页码：582.e1-582.e9
- 全文大小：548 K
ObjectiveConsistent epidemiologic evidence suggests that acute infections increase the risk for acute cardiovascular events. We tested in humans whether activation of peripheral leukocytes in reaction to the administration of recombinant human C-reactive protein (rhCRP) may provide a mechanism for infectious diseases to promote atherosclerotic disease.Methods and Results
By using quantitative real-time polymerase chain reaction analysis, whole-blood expression profiles were analyzed for 95 inflammatory markers before and after infusion of 1.25 mg/kg rhCRP in 5 male volunteers. Relevant transcript levels were measured at baseline and 4 and 8 hours after rhCRP-infusion. CRP caused significant up-regulation of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, plasminogen activator urokinase, macrophage inflammatory protein 1α, and nuclear factor of kappa B inhibitor mRNAs in peripheral leukocytes. mRNA up-regulation of MMP-9 and MCP-1 was 17- and 11-fold, respectively. The corresponding increase in plasma protein levels of MMP-9 (78 ± 32 ng/mL to 109 ± 41 ng/mL; P = .014) and MCP-1 (312 ± 92 pg/mL to 2590 ± 898 pg/mL; P = .007) closely mirrored mRNA findings. Also, in whole-blood culture stimulation assays, CRP induced proinflammatory changes. Notably, heat inactivation abolished the capacity of CRP to evoke these proinflammatory changes, excluding a role for contaminants within the purified CRP preparation.
Conclusion
CRP elicits activation of peripheral leukocytes with ensuing secretion of plaque-destabilizing mediators. These findings are consistent with the hypothesis that infectious diseases trigger manifestations of atherosclerosis, in which CRP elevation might contribute to the onset of cardiovascular events.