Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10769224 | Biochemical and Biophysical Research Communications | 2005 | 6 Pages |
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 Gi-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.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Wojciech Kalas, Petr Klement, Janusz Rak,