title: Cardio-hepatic metabolic derangements and valproic acid.
abstract: 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 target cells.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Mazzoccoli
authors.forename: Calogero
authors.initials: C
authors.lastname: Longhitano
authors.affiliation: Institute of Hepatology, The Foundation for Liver Research, 69-75 Cheney Mews, London, WC1E 6HX, United Kingdom. m.vinciguerra@researchinliver.org.uk.
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects; D018692:Antimanic Agents / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000503:physiopathology; D044127:Epigenesis, Genetic / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000503:physiopathology; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors; D006801:Humans; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D018692:Antimanic Agents; D014635:Valproic Acid; D056284:Histone Deacetylase 1