TY - JOUR
T1 - Transient interaction of activated platelets with endothelial cells induces expression of monocyte-chemoattractant protein-1 via a p38 mitogen-activated protein kinase mediated pathway
T2 - Implications for atherogenesis
AU - Dickfeld, Timm
AU - Lengyel, Ernst
AU - May, Andreas E.
AU - Massberg, Steffen
AU - Brand, Korbinian
AU - Page, Sharon
AU - Thielen, Christiane
AU - Langenbrink, Kirsten
AU - Gawaz, Meinrad
PY - 2001
Y1 - 2001
N2 - Objective: Activated platelets induce alterations of chemotactic and adhesive properties of endothelial cells, a critical initial step in atherogenesis. We investigated the effect of transient interaction of activated platelets with cultured human umbilical vein endothelial cells (HUVECs) on secretion of monocyte chemoattractant protein-1 (MCP-1), a key molecule in monocyte chemotaxis and transmigration. Methods and results: Transient interaction of α-thrombin-activated platelets with endothelial cells for 10-120 min substantially induced endothelial secretion of MCP-1, monocyte chemotaxis and adhesion to HUVECs. Platelet-induced secretion of MCP-1 and monocyte-endothelium adhesion was reduced by the MAP kinase p38-specific inhibitor SB203580, but not by other kinase inhibitors including PD98059, wortmannin, or rapamycin. In addition, activated platelets induced transcription of a luciferase reporter construct containing a MCP-1 promotor, an effect that could be inhibited by SB203580. Overexpression of dominant-negative mutants of MAP kinase p38, CSBP2-(D168A) and CSBP2-(T180E,Y182E) reduced platelet-induced expression of MCP-1. Conclusions: Activation of the p38 MAP kinase and consecutive endothelial secretion of MCP-1 induced through transient interaction of activated platelets might play an important role in atherogenesis. (C) 2001 Elsevier Science B.V.
AB - Objective: Activated platelets induce alterations of chemotactic and adhesive properties of endothelial cells, a critical initial step in atherogenesis. We investigated the effect of transient interaction of activated platelets with cultured human umbilical vein endothelial cells (HUVECs) on secretion of monocyte chemoattractant protein-1 (MCP-1), a key molecule in monocyte chemotaxis and transmigration. Methods and results: Transient interaction of α-thrombin-activated platelets with endothelial cells for 10-120 min substantially induced endothelial secretion of MCP-1, monocyte chemotaxis and adhesion to HUVECs. Platelet-induced secretion of MCP-1 and monocyte-endothelium adhesion was reduced by the MAP kinase p38-specific inhibitor SB203580, but not by other kinase inhibitors including PD98059, wortmannin, or rapamycin. In addition, activated platelets induced transcription of a luciferase reporter construct containing a MCP-1 promotor, an effect that could be inhibited by SB203580. Overexpression of dominant-negative mutants of MAP kinase p38, CSBP2-(D168A) and CSBP2-(T180E,Y182E) reduced platelet-induced expression of MCP-1. Conclusions: Activation of the p38 MAP kinase and consecutive endothelial secretion of MCP-1 induced through transient interaction of activated platelets might play an important role in atherogenesis. (C) 2001 Elsevier Science B.V.
KW - Atherosclerosis
KW - Complement activation
KW - Endothelial function
KW - Platelets
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U2 - 10.1016/S0008-6363(00)00220-0
DO - 10.1016/S0008-6363(00)00220-0
M3 - Article
C2 - 11121811
AN - SCOPUS:0034751239
SN - 0008-6363
VL - 49
SP - 189
EP - 199
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -