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 alpha-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.
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 alpha-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.
Authors: Amala P Chirumamilla; Akiko Maehara; Gary S Mintz; Roxana Mehran; Sunil Kanwal; Giora Weisz; Ahmed Hassanin; Diaa Hakim; Ning Guo; Usman Baber; Robert Pyo; Jeffrey W Moses; Martin Fahy; Jason C Kovacic; George D Dangas Journal: JACC Cardiovasc Imaging Date: 2012-05
Authors: Zhi-Yong Lu; Liselotte E Jensen; Yuehua Huang; Carmel Kealey; Ian A Blair; Alexander S Whitehead Journal: Atherosclerosis Date: 2008-12-13 Impact factor: 5.162
Authors: R Carnevale; L Loffredo; C Nocella; S Bartimoccia; T Bucci; E De Falco; M Peruzzi; I Chimenti; G Biondi-Zoccai; P Pignatelli; F Violi; G Frati Journal: Oxid Med Cell Longev Date: 2014-08-07 Impact factor: 6.543