Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.

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 presen...

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Main Authors: Jakob Karén, Alejandro Rodriguez, Tomas Friman, Lennart Dencker, Christian Sundberg, Birger Scholz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3178576?pdf=render
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author Jakob Karén
Alejandro Rodriguez
Tomas Friman
Lennart Dencker
Christian Sundberg
Birger Scholz
author_facet Jakob Karén
Alejandro Rodriguez
Tomas Friman
Lennart Dencker
Christian Sundberg
Birger Scholz
author_sort Jakob Karén
collection DOAJ
description 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.
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spelling doaj.art-8077904b187547388e02e5df0ee2a8332022-12-22T03:44:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2495410.1371/journal.pone.0024954Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.Jakob KarénAlejandro RodriguezTomas FrimanLennart DenckerChristian SundbergBirger ScholzMicrovascular 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.http://europepmc.org/articles/PMC3178576?pdf=render
spellingShingle Jakob Karén
Alejandro Rodriguez
Tomas Friman
Lennart Dencker
Christian Sundberg
Birger Scholz
Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
PLoS ONE
title Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
title_full Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
title_fullStr Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
title_full_unstemmed Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
title_short Effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro.
title_sort effects of the histone deacetylase inhibitor valproic acid on human pericytes in vitro
url http://europepmc.org/articles/PMC3178576?pdf=render
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