title: Downregulation of the angiogenesis inhibitor thrombospondin 1 in fibroblasts exposed to platelets and their related phospholipids.
abstract: Platelets play many important roles in maintenance and formation of blood vessels. The latter is usually attributed to release of direct acting proangiogenic influences, e.g., vascular endothelial growth factor, sphingosine 1 phosphate, and other mediators, though their effects are normally opposed by endogenous angiogenesis inhibitors, including thrombospondin 1 (TSP-1/THSP1). Hence downregulation of TSP-1 is regarded as an important step in the generation of the pro-angiogenic (tumor) stroma. Here we report that platelets induce marked downregulation of TSP-1 (gene transcription and protein) in mouse dermal fibroblasts. This effect is: (i) blocked by inhibitors of sphingosine kinase, (ii) unaffected by inhibitors of G(i)-proteins (pertussis toxin), (iii) recapitulated by sphingosine, (iv) can also be induced by lysophosphatidic acid. These observations suggest a hitherto unappreciated, indirect role of platelets and their phospholipids in angiogenesis, i.e., proangiogenic conditioning of connective tissue stroma through lowering TSP-1 expression.
authors: Henderson Research Centre, Experimental Thrombosis Research, McMaster University, Hamilton, Ont., Canada.
authors: Wojciech
authors: W
authors: Kalas
authors: Petr
authors: P
authors: Klement
authors: Janusz
authors: J
authors: Rak
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism* / Q000494:pharmacology; D013107:Sphingolipids / Q000378:metabolism* / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism*
chemical_list: D010743:Phospholipids; D013107:Sphingolipids; D019700:Thrombospondin 1