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Heparan-dependent endothelial antithrombin binding is increased by butyrate
A C Justus1, A M Hoggatt, W P Faulk
1Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202, USA.
Thrombosis Research
|October 15, 1995
Summary
Short-chain fatty acids like n-butyrate increase endothelial cell binding of antithrombin (AT). This process, dependent on heparan sulfate, alters heparin biosynthesis and activates endothelial cells.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Heparin biosynthesis is regulated by N-deacetylation, a process inhibited by n-butyrate.
- Inhibition of N-deacetylation leads to mast cells producing heparins with high antithrombin (AT) affinity.
Purpose of the Study:
- To investigate the effect of short-chain fatty acids (SCFAs) on endothelial cell binding of AT.
- To explore the role of heparan sulfate in SCFA-mediated AT binding.
Main Methods:
- Endothelial cells were cultured in media supplemented with various SCFAs.
- Antithrombin (AT) binding was measured using flow cytometry.
- The role of heparan sulfate was assessed by pre-treating cells with heparinase.
Main Results:
- Isobutyric, propionic, and valeric acids significantly increased AT binding to endothelial cells.
- N-butyric acid was the most effective SCFA in enhancing AT binding.
- Heparinase treatment significantly decreased AT binding, confirming heparan sulfate dependence.
- SCFA treatment led to increased expression of intercellular adhesion molecule-1 (ICAM-1), a marker of endothelial activation.
Conclusions:
- Inhibition of N-deacetylation during heparan biosynthesis by SCFAs alters heparan sulfate structure.
- These alterations affect AT binding affinity and endothelial cell activation.
- SCFAs represent a novel mechanism influencing endothelial cell function and anticoagulation properties.