Cardio-Hepatic Metabolic Derangements and Valproic Acid
Gianluigi Mazzoccoli, Calogero Longhitano and Manlio Vinciguerra
Affiliation: Institute of Hepatology, The Foundation for Liver Research, 69-75 Cheney Mews, London, WC1E 6HX, United Kingdom.
Keywords: Epigenetics, heart, histone deacetylases, lipid metabolism, liver, valproic acid.
Valproic acid (VPA) is an anti-epileptic and mood-stabilizing compound successfully used in the clinics since
many decades. During the last few years, research on VPA revitalized. VPA has profound impact on nuclear chromatin
structure in target cells by impinging on epigenetic mechanisms such as inhibition of histone deacetylase HDAC1, with
implications for HIV and cancer treatment, and for the direct reprogramming in generation of induced pluripotent stem
(iPS) cells. VPA can thus act at multiple levels and in several cellular systems. In addition to its established applications
for the treatment of neurological and psychiatric disorders, and its newly discovered epigenetic mechanisms of action, the
peripheral metabolic effects of VPA administration, in particular impinging on the heart and on the liver, are now starting
to be understood. These have important consequences for the management of therapy and also for investigation purposes.
The aim of this article is on one hand to summarize the emerging knowledge on the role of VPA during the occurrence of
cardio-metabolic dysfunctions and on the other hand to describe concisely the VPA-induced epigenetic modifications in
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