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http://purl.uniprot.org/citations/26586662http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26586662http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Hyaluronan (HA) is a polymeric glucosaminoglycan that forms a provisional extracellular matrix in diseased vessels. HA is synthesized by 3 different HA synthases (HAS1, HAS2, and HAS3). Aim of this study was to unravel the role of the HAS3 isoenzyme during experimental neointimal hyperplasia.

Approach and results

Neointimal hyperplasia was induced in Has3-deficient mice by ligation of the carotid artery. HA in the media of Has3-deficient mice was decreased 28 days after ligation, and neointimal hyperplasia was strongly inhibited. However, medial and luminal areas were unaffected. Cell density, proliferation, and apoptosis were not altered, suggesting a proportional decrease of both, the number of cells and extracellular matrix. In addition, endothelial function as determined by acetylcholine-induced relaxation of aortic rings, immunoblotting of endothelial nitric oxide synthase, and arterial blood pressure were not affected. Furthermore, the oxidative stress response was not affected as determined in total protein extracts from aortae. Transcriptome analysis comparing control versus ligated carotid arteries hinted toward a mitigated differential regulation of various signaling pathways in Has3-deficient mice in response to ligation that were related to vascular smooth muscle cell (VSMC) migration, including focal adhesions, integrins, mitogen-activated protein kinase, and phosphatidylinositol signaling system. Lentiviral overexpression of HAS3 in VSMC supported the migratory phenotype of VSMC in response to platelet-derived growth factor BB in vitro. Accordingly, knockdown of HAS3 reduced the migratory response to platelet-derived growth factor BB and in addition decreased the expression of PDGF-B mRNA.

Conclusions

HAS3-mediated HA synthesis after vessel injury supports seminal signaling pathways in activation of VSMC, increases platelet-derived growth factor BB-mediated migration, and in turn enhances neointimal hyperplasia in vivo."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.115.306607"xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Muller J."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Savani R.C."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Homann S."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Dai G."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Hartwig S."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Kohrer K."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Deenen R."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Fischer J.W."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Lehr S."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Kojda G."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Grandoch M."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Suvorava T."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Twarock S."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Kretschmer I."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Rabausch B."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/author"Kiene L.S."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/pages"e9-16"xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/title"Deletion of Hyaluronan Synthase 3 Inhibits Neointimal Hyperplasia in Mice."xsd:string
http://purl.uniprot.org/citations/26586662http://purl.uniprot.org/core/volume"36"xsd:string
http://purl.uniprot.org/citations/26586662http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26586662
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