title: Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
abstract: Microvascular pericytes are of key importance in neoformation of blood vessels, in stabilization of newly formed vessels as well as maintenance of angiostasis in resting tissues. Furthermore, pericytes are capable of differentiating into pro-fibrotic collagen type I producing fibroblasts. The present study investigates the effects of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) on pericyte proliferation, cell viability, migration and differentiation. The results show that HDAC inhibition through exposure of pericytes to VPA in vitro causes the inhibition of pericyte proliferation and migration with no effect on cell viability. Pericyte exposure to the potent HDAC inhibitor Trichostatin A caused similar effects on pericyte proliferation, migration and cell viability. HDAC inhibition also inhibited pericyte differentiation into collagen type I producing fibroblasts. Given the importance of pericytes in blood vessel biology a qPCR array focusing on the expression of mRNAs coding for proteins that regulate angiogenesis was performed. The results showed that HDAC inhibition promoted transcription of genes involved in vessel stabilization/maturation in human microvascular pericytes. The present in vitro study demonstrates that VPA influences several aspects of microvascular pericyte biology and suggests an alternative mechanism by which HDAC inhibition affects blood vessels. The results raise the possibility that HDAC inhibition inhibits angiogenesis partly through promoting a pericyte phenotype associated with stabilization/maturation of blood vessels.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Karén
authors.forename: Alejandro
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Tomas
authors.initials: T
authors.lastname: Friman
authors.forename: Lennart
authors.initials: L
authors.lastname: Dencker
authors.forename: Christian
authors.initials: C
authors.lastname: Sundberg
authors.forename: Birger
authors.initials: B
authors.lastname: Scholz
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010641:Phenotype; D010920:Placenta / Q000187:drug effects; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid