title: Monomeric C-reactive protein alters fibrin clot properties on endothelial cells.
abstract: Elevated plasma levels of C-reactive protein (CRP) are independently associated with increased risk of atherothrombosis. Several lines of evidence suggest that CRP has prothrombogenic effects on injured vessel wall(s) by enhancing tissue factor (TF) expression. Abnormal fibrin formation is correlated with increased thrombotic risk. However, the impact of localized, cell surface-driven in situ tissue factor generation by CRP on clot dynamics and fibrin architecture has not previously been evaluated. We examined the impact of native CRP and modified or monomeric CRP (mCRP) on the fibrin formation and structure in Human Umbilical Vein Endothelial Cells (HUVECs). Fibrin formation and structure were examined using laser scanning confocal microscopy. Incubation with mCRP on the cell surface had faster fibrin polymerization by the analysis of turbidimetry. Confocal microscopy of fibrin clots showed a significantly increased density in the treatment of mCRP compared with native CRP and control in the proximal versus distal relationship to the cell surface. The increased expression and activity of TF on the cell surface was observed by addition of mCRP. Blockage of tissue factor and lipid rafts significantly reduced the density of fibrin network produced by mCRP-stimulated endothelial cells. mCRP changes clot dynamics and alters fibrin architecture by enhancing TF on the endothelial cell surface. These results support the concept that elevated CRP levels may induce fibrinolytic resistance and endothelial dysfunction by altering fibrin clot structure.
authors.affiliation: Drug Discovery Research Center, Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Meiping
authors.initials: M
authors.lastname: Ren
authors.forename: Mao
authors.initials: M
authors.lastname: Luo
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Luo
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
mesh_terms: D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000096:biosynthesis*; D013927:Thrombosis / Q000097:blood* / Q000473:pathology
chemical_list: D011994:Recombinant Proteins; D005337:Fibrin; D002097:C-Reactive Protein; D013917:Thrombin