NDLI: Histone deacetylase inhibitors stimulate tissue-type plasminogen activator production in vascular endothelial cells

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Histone deacetylase inhibitors stimulate tissue-type plasminogen activator production in vascular endothelial cells

Content Provider	Semantic Scholar
Author	Larsson, Pia Nygård Bergh, Niklas Lu, Emma Xuchun Ulfhammer, Erik Magnusson, Mia Wåhlander, Karin Karlsson, Lena Jern, Sverker
Copyright Year	2012
Abstract	A reduced capacity for acute tissue-type plasminogen activator (t-PA) release is likely to be associated with an impaired endogenous defense against intravascular thrombosis. Efficient approaches to pharmacologically restore a defective t-PA release have been lacking, but recent observations suggest that histone deacetylase inhibitors (HDACis) enhance t-PA production in vitro. HDACis have diverse chemical structures and different HDAC-enzyme sub-class targeting. We here compared the effects of several clinically used HDACis on t-PA production in endothelial cells. Human umbilical vein endothelial cells were exposed to a panel of 11 different HDACis and t-PA mRNA and protein levels were quantified. All HDACis dose-dependently stimulated t-PA mRNA and protein expression with similar maximal efficacy but with different potencies. Already at low concentrations, the majority of inhibitors caused significant and sustained effects on t-PA production. In addition, selected HDACis were capable of normalizing t-PA production when suppressed by the inflammatory cytokine TNF-α. We conclude that HDACis targeting classical HDAC enzymes are powerful inducers of t-PA expression in cultured endothelial cells and could be promising candidates for pharmacological modulation of endogenous fibrinolysis in man.
Starting Page	185
Ending Page	192
Page Count	8
File Format	PDF HTM / HTML
DOI	10.1007/s11239-012-0831-6
PubMed reference number	23229086
Journal	Medline
Volume Number	35
Alternate Webpage(s)	http://file2.selleckchem.com/citations/Entinostat-Vorinostat-Belinostat-Givinostat-LBH589-JNJ26481585-SB939-Mocetinostat-staurosporine-J-Thromb-Thrombolysis-20140506.pdf
Alternate Webpage(s)	https://doi.org/10.1007/s11239-012-0831-6
Journal	Journal of Thrombosis and Thrombolysis
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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