C-reactive protein decreases tissue plasminogen activator activity in human aortic endothelial cells: Evidence that C-reactive protein is a procoagulant

Uma Singh, Sridevi Devaraj, Ishwarlal Jialal

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Objective - C-reactive protein (CRP) can promote atherothrombosis by decreasing endothelial nitric oxide synthase and prostacyclin, and by stimulating both plasminogen activator inhibitor-1 in endothelial cells and tissue factor in mononuclear cells. Plasminogen activator-1, a marker of fibrinolysis, is the primary inhibitor of tissue plasminogen activator (tPA). Thus, we tested the effect of CRP on tPA in human aortic endothelial cells. Methods and Results - Incubation of human aortic endothelial cells with CRP (≥12.5 μg/mL) significantly decreased tPA antigen and activity. Adenyl cyclase inhibitors, an endothelin receptor antagonist, superoxide dismutase, and a nitric oxide donor failed to reverse the effect of CRP on tPA. CRP increased interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Neutralization of both IL-1β and TNFα reversed the inhibition of tPA by CRP. Furthermore, in volunteers that have high CRP levels, euglobulin clot lysis time was significantly increased compared with those that have low CRP levels, providing further evidence that high CRP levels are associated with a procoagulant state. Conclusions - CRP inhibits tPA activity via generation of proinflammatory cytokines (IL-1β and TNFα). This study provides additional novel data that CRP is a procoagulant and has implications for atherothrombosis.

Original languageEnglish (US)
Pages (from-to)2216-2221
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume25
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • C-reactive protein
  • Endothelial cells
  • Inflammation
  • Procoagulant
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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