PMID- 14512080 OWN - NLM STAT- MEDLINE DCOM- 20040525 LR - 20190727 IS - 0049-3848 (Print) IS - 0049-3848 (Linking) VI - 110 IP - 4 DP - 2003 Jun 1 TI - Activated platelets trigger an inflammatory response and enhance migration of aortic smooth muscle cells. PG - 187-94 AB - OBJECTIVE: Exposure of the subendothelium to flowing blood following rupture of atherosclerotic lesions or during balloon angioplasty initiates platelet adhesion to the vascular wall. Because activated platelets release proinflammatory mediators (e.g., interleukin (IL)-1beta) and secrete growth factors, platelet adhesion to the subendothelial matrix might contribute to the recruitment of inflammatory cells and promote migration and proliferation of vascular smooth muscle cells (SMCs). METHODS AND RESULTS: Here, we demonstrate that incubation of cultured monolayers of aortic SMCs with alpha-thrombin-activated platelets significantly enhances the secretion of monocyte chemoattractant protein-1 (MCP-1) (P<0.05) and promotes SMC migration (P<0.05). Platelet-induced secretion of MCP-1 was abolished by anti-IL-1alpha and beta monoclonal antibodies or the IL-1 receptor antagonist (IL-1RA). In contrast, platelet-mediated SMC migration was attenuated only by anti-platelet-derived growth factor (PDGF)-mAb but not by IL-1RA. Correspondingly, recombinant human interleukin-1 (rhIL-1) beta increased MCP release by SMCs but had no effect on SMC migration. Platelet-mediated MCP secretion by SMCs involved the activation and nuclear translocation of the transcription factor nuclear factor-kappaB (NF-kappaB). CONCLUSION: Therefore, platelet adhesion to the subendothelium increases the chemotactic and migratory properties of SMC and is likely to contribute substantially to the process of atherosclerosis and vessel (re-)stenosis. FAU - Massberg, Steffen AU - Massberg S AD - Medizinische Klinik and Deutsches Herzzentrum, Technische Universitat Munchen, Lazarettstrasse 36, 80636 Munich, Germany. massberg@dhm.mhn.de FAU - Vogt, Felix AU - Vogt F FAU - Dickfeld, Timm AU - Dickfeld T FAU - Brand, Korbinian AU - Brand K FAU - Page, Sharon AU - Page S FAU - Gawaz, Meinrad AU - Gawaz M LA - eng PT - Journal Article PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Chemokine CCL2) SB - IM MH - *Aorta/cytology MH - Blood Platelets/*metabolism MH - Cell Adhesion/physiology MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Humans MH - Inflammation MH - Muscle, Smooth, Vascular/*metabolism MH - *Platelet Activation EDAT- 2003/09/27 05:00 MHDA- 2004/05/27 05:00 CRDT- 2003/09/27 05:00 PHST- 2003/09/27 05:00 [pubmed] PHST- 2004/05/27 05:00 [medline] PHST- 2003/09/27 05:00 [entrez] AID - S0049384803003426 [pii] AID - 10.1016/s0049-3848(03)00342-6 [doi] PST - ppublish SO - Thromb Res. 2003 Jun 1;110(4):187-94. doi: 10.1016/s0049-3848(03)00342-6.