C-Reactive Protein Decreases Tissue Plasminogen Activator Activity in Human Aortic Endothelial Cells
- 1 October 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 25 (10), 2216-2221
- https://doi.org/10.1161/01.atv.0000183718.62409.ea
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.Keywords
This publication has 37 references indexed in Scilit:
- An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusionJournal of the American College of Cardiology, 2005
- Human C-Reactive Protein Increases Cerebral Infarct Size after Middle Cerebral Artery Occlusion in Adult RatsJournal of Cerebral Blood Flow & Metabolism, 2004
- C-Reactive Protein Promotes Monocyte Chemoattractant Protein-1—Mediated Chemotaxis Through Upregulating CC Chemokine Receptor 2 Expression in Human MonocytesCirculation, 2004
- Effect of C-reactive protein on chemokine expression in human aortic endothelial cellsJournal of Molecular and Cellular Cardiology, 2004
- Alcohol‐Induced Upregulation of Plasminogen Activators and Fibrinolytic Activity in Cultured Human Endothelial CellsAlcohol: Clinical and Experimental Research, 1998
- Tissue Plasminogen Activator for Acute Ischemic StrokeNew England Journal of Medicine, 1995
- Complex intracellular signal transduction regulates tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) synthesis in cultured human umbilical vein endotheliumScandinavian Journal of Clinical and Laboratory Investigation, 1995
- Endothelin modulation of tissue plasminogen activator release from human vascular endothelial cells in cultureBlood Coagulation & Fibrinolysis, 1992
- Inhibition of endothelial secretion of tissue-type plasminogen activator and its rapid inhibitor by agents which increase intracellular cyclic AMPBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1989
- C-reactive protein is protective against Streptococcus pneumoniae infection in mice.The Journal of Experimental Medicine, 1981