Valproic acid attenuates hyperglycemia-induced complement and coagulation cascade gene expression

Felisbino, Marina Barreto, Ziemann, Mark, Khurana, Ishant, de Oliveira, Camila Borges Martins, Mello, Maria Luiza S. and El-Osta, Assam 2018, Valproic acid attenuates hyperglycemia-induced complement and coagulation cascade gene expression, bioRxiv, doi: 10.1101/253591.

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Title Valproic acid attenuates hyperglycemia-induced complement and coagulation cascade gene expression
Author(s) Felisbino, Marina Barreto
Ziemann, MarkORCID iD for Ziemann, Mark orcid.org/0000-0002-7688-6974
Khurana, Ishant
de Oliveira, Camila Borges Martins
Mello, Maria Luiza S.
El-Osta, Assam
Journal name bioRxiv
Total pages 27
Publisher Cold Spring Harbor Laboratory Press
Place of publication Woodbury, N. Y.
Publication date 2018-01-25
Keyword(s) HDAC inhibitor
hyperglycemia
transcriptome
valporic acid
Summary Atherothrombosis remains the leading cause of morbidity and mortality in patients diagnosed with diabetes mellitus, but the molecular mechanisms underpinning this remain unresolved. As the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is an interest in understanding the mechanisms of hepatic cell activation under hyperglycemia and whether this can be attenuated pharmacologically. We have previously shown that hyperglycemia stimulates major changes in chromatin organisation and metabolism in hepatocytes, and that the histone deacetylase inhibitor valproic acid (VPA; IUPAC: 2-propylpentanoic acid) is able to reverse some of these metabolic changes. In this study, we used deep transcriptome sequencing to show that VPA attenuates hyperglycemia-induced activation of complement and coagulation cascade genes. These findings reveal a novel mechanism of VPA protection against hyperglycemia, which might improve the therapeutic approaches for diabetes.
Language eng
DOI 10.1101/253591
Copyright notice ©2018, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30113081

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