Transient interaction of activated platelets with endothelial cells induces expression of monocyte-chemoattractant protein-1 via a p38 mitogen-activated protein kinase mediated pathway: Implications for atherogenesis

Timm Dickfeld, Ernst Lengyel, Andreas E. May, Steffen Massberg, Korbinian Brand, Sharon Page, Christiane Thielen, Kirsten Langenbrink, Meinrad Gawaz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)189-199
Number of pages11
JournalCardiovascular Research
Volume49
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Atherosclerosis
  • Complement activation
  • Endothelial function
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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