Thrombospondin 1 Blocks Growth of Endothelial Cells in Systemic Sclerosis
Author Information
Author(s): Morgan-Rowe Luke, Nikitorowicz Joanna, Shiwen Xu, Leask Andrew, Tsui Janice, Abraham David, Stratton Richard
Primary Institution: Centre for Rheumatology Research and Connective Tissue Diseases, The Royal Free Hospital Campus, University College London
Hypothesis
The failure of angiogenesis in systemic sclerosis may be due to an upregulation of antiangiogenic factors produced by hypoxic tissues.
Conclusion
Thrombospondin 1 is released in high concentrations by hypoxic endothelial cells and blocks proliferation and induces apoptosis in microvascular endothelial cells.
Supporting Evidence
- TSP-1 was expressed in high concentrations in the hypoxic media.
- Depletion of TSP-1 from the media reduced the antiproliferative effect.
- Recombinant TSP-1 blocked the proliferation of endothelial cells in a dose-dependent manner.
- Immunohistochemistry revealed significantly higher TSP-1 expression in the skin of patients with systemic sclerosis compared to healthy controls.
Takeaway
In patients with systemic sclerosis, a protein called thrombospondin 1 is found in high amounts and stops blood vessel cells from growing, which can make it hard for the body to heal.
Methodology
Human microvascular endothelial cells were cultured in normoxic and hypoxic conditions, and the effects of conditioned media on cell proliferation were assessed.
Participant Demographics
Patients with systemic sclerosis and healthy controls.
Statistical Information
P-Value
<0.004
Statistical Significance
p<0.004
Digital Object Identifier (DOI)
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