Abstract | BACKGROUND: OBJECTIVES: We studied transgenic (Tg) mice expressing human CRP in a VG model to explore in vivo cause-and-effect relationships between CRP and TF, PAI-1, and VG thrombosis. METHODS: Vein segments from wild-type (WT) and CRP-Tg donors were transplanted into carotid arteries of WT and CRP-Tg recipients. VGs were analyzed 1-4 weeks later. RESULTS: Human CRP accumulated in VGs during the first 4 weeks after surgery, but appeared to originate exclusively from systemic sources, rather than local production. Human CRP significantly increased TF gene expression, protein concentration and activity in VGs. Human CRP also increased PAI-1 concentrations in VGs, although only in vascular endothelial cells. Human CRP stimulated macrophage migration, invasion into VGs, and TF expression. Fibrin deposition was significantly greater in VGs of CRP-Tg mice than in WT controls. CONCLUSIONS: CRP accumulates in VGs early after surgery, originating from systemic sources rather than local synthesis. Human CRP promotes TF and PAI-1 expression in VGs, although with different expression patterns. Human CRP stimulates macrophage invasion and fibrin deposition within VGs. These results suggest that CRP induces pathologic changes in VGs that contribute to early VG occlusion.
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Authors | Y Ji, P M Fish, T L Strawn, A W Lohman, J Wu, A J Szalai, W P Fay |
Journal | Journal of thrombosis and haemostasis : JTH
(J Thromb Haemost)
Vol. 12
Issue 10
Pg. 1667-77
(Oct 2014)
ISSN: 1538-7836 [Electronic] England |
PMID | 25081365
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | © 2014 International Society on Thrombosis and Haemostasis. |
Chemical References |
- Chlorides
- Ferric Compounds
- Plasminogen Activator Inhibitor 1
- Recombinant Proteins
- SERPINE1 protein, human
- Fibrin
- C-Reactive Protein
- Thromboplastin
- ferric chloride
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Topics |
- Animals
- C-Reactive Protein
(metabolism)
- Cell Movement
- Chlorides
(chemistry)
- Coronary Artery Bypass
- Ferric Compounds
(chemistry)
- Fibrin
(metabolism)
- Humans
- Macrophages
(metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Plasminogen Activator Inhibitor 1
(metabolism)
- Recombinant Proteins
(metabolism)
- Thromboplastin
(metabolism)
- Transgenes
- Veins
(transplantation)
- Venous Thrombosis
(blood)
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