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000014547 0247_ $$2pmid$$apmid:21164077
000014547 0247_ $$2DOI$$a10.1161/ATVBAHA.110.219105
000014547 0247_ $$2WOS$$aWOS:000287409900023
000014547 037__ $$aPreJuSER-14547
000014547 041__ $$aeng
000014547 082__ $$a610
000014547 084__ $$2WoS$$aHematology
000014547 084__ $$2WoS$$aPeripheral Vascular Disease
000014547 1001_ $$0P:(DE-HGF)0$$aDangwal, S.$$b0
000014547 245__ $$aHigh glucose enhances thrombin responses via protease-activated receptor-4 in human vascular smooth muscle cells
000014547 260__ $$aPhiladelphia, Pa.$$bLippincott, Williams & Wilkins$$c2011
000014547 300__ $$a624 - 633
000014547 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
000014547 3367_ $$2DataCite$$aOutput Types/Journal article
000014547 3367_ $$00$$2EndNote$$aJournal Article
000014547 3367_ $$2BibTeX$$aARTICLE
000014547 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000014547 3367_ $$2DRIVER$$aarticle
000014547 440_0 $$023721$$aArteriosclerosis, Thrombosis, and Vascular Biology$$v31$$x1079-5642$$y3
000014547 500__ $$aThis study was supported in part by the Deutsche Forschungsgemeinschaft (SFB 612, Project B11), the Anna Wunderlich-Ernst Juhling Stiftung (Dusseldorf, Germany), and the Forschungsgruppe Herz-Kreislauf eV (Monheim, Germany).
000014547 520__ $$aDiabetes is associated with vascular remodeling and increased thrombin generation. Thrombin promotes vascular smooth muscle cell (SMC) mitogenesis and migration via protease-activated receptors (PAR)-1, PAR-3, and PAR-4. We investigated the effect of high glucose on expression and function of vascular thrombin receptors.In human vascular SMCs, high glucose (25 versus 5.5 mmol/L) induced a rapid and sustained increase in PAR-4 mRNA, protein, and cell surface expression. PAR-1 and PAR-3 expression were not changed. High glucose pretreatment (48 hours) enhanced thrombin or PAR-4-activating peptide but not PAR-1-activating peptide evoked intracellular calcium mobilization, migration, and tumor necrosis factor α gene expression. This enhancement of thrombin-stimulated migration and gene expression by high glucose was abolished by endogenous PAR-4 knockdown. PAR-4 regulation was prevented by inhibition of protein kinase (PK)C-β and -δ isoforms or nuclear factor (NF)κB. Nuclear translocation of NFκB in high glucose-stimulated SMCs led to PKC-dependent NFκB binding to the PAR-4 promoter in a chromatin immunoprecipitation assay. Furthermore, in situ hybridization and immunohistochemistry confirmed high abundance of PAR-4 in human diabetic vessels as compared with nondiabetic vessels.High glucose enhances SMC responsiveness to thrombin through transcriptional upregulation of PAR-4, mediated via PKC-β, -δ, and NFκB. This may play an important role in the vascular complications of diabetes.
000014547 536__ $$0G:(DE-Juel1)FUEK505$$2G:(DE-HGF)$$aBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$cP45$$x0
000014547 588__ $$aDataset connected to Web of Science, Pubmed
000014547 65320 $$2Author$$adiabetes mellitus
000014547 65320 $$2Author$$athrombin
000014547 65320 $$2Author$$avascular muscle
000014547 65320 $$2Author$$aprotease-activated receptors
000014547 650_2 $$2MeSH$$aBinding Sites
000014547 650_2 $$2MeSH$$aCalcium: metabolism
000014547 650_2 $$2MeSH$$aCalcium Signaling
000014547 650_2 $$2MeSH$$aCell Movement
000014547 650_2 $$2MeSH$$aCells, Cultured
000014547 650_2 $$2MeSH$$aChromatin Immunoprecipitation
000014547 650_2 $$2MeSH$$aDiabetic Angiopathies: genetics
000014547 650_2 $$2MeSH$$aDiabetic Angiopathies: metabolism
000014547 650_2 $$2MeSH$$aGlucose: metabolism
000014547 650_2 $$2MeSH$$aHumans
000014547 650_2 $$2MeSH$$aImmunohistochemistry
000014547 650_2 $$2MeSH$$aIn Situ Hybridization
000014547 650_2 $$2MeSH$$aMuscle, Smooth, Vascular: metabolism
000014547 650_2 $$2MeSH$$aMyocytes, Smooth Muscle: metabolism
000014547 650_2 $$2MeSH$$aNF-kappa B: metabolism
000014547 650_2 $$2MeSH$$aPromoter Regions, Genetic
000014547 650_2 $$2MeSH$$aProtein Kinase C: antagonists & inhibitors
000014547 650_2 $$2MeSH$$aProtein Kinase C: metabolism
000014547 650_2 $$2MeSH$$aProtein Kinase C-delta: genetics
000014547 650_2 $$2MeSH$$aProtein Kinase C-delta: metabolism
000014547 650_2 $$2MeSH$$aProtein Kinase Inhibitors: pharmacology
000014547 650_2 $$2MeSH$$aRNA Interference
000014547 650_2 $$2MeSH$$aRNA, Messenger: metabolism
000014547 650_2 $$2MeSH$$aReceptor, PAR-1: metabolism
000014547 650_2 $$2MeSH$$aReceptors, Thrombin: genetics
000014547 650_2 $$2MeSH$$aReceptors, Thrombin: metabolism
000014547 650_2 $$2MeSH$$aThrombin: metabolism
000014547 650_2 $$2MeSH$$aTime Factors
000014547 650_2 $$2MeSH$$aTranscriptional Activation
000014547 650_2 $$2MeSH$$aTumor Necrosis Factor-alpha: genetics
000014547 650_2 $$2MeSH$$aUp-Regulation
000014547 650_7 $$00$$2NLM Chemicals$$aNF-kappa B
000014547 650_7 $$00$$2NLM Chemicals$$aProtein Kinase Inhibitors
000014547 650_7 $$00$$2NLM Chemicals$$aRNA, Messenger
000014547 650_7 $$00$$2NLM Chemicals$$aReceptor, PAR-1
000014547 650_7 $$00$$2NLM Chemicals$$aReceptors, Thrombin
000014547 650_7 $$00$$2NLM Chemicals$$aTumor Necrosis Factor-alpha
000014547 650_7 $$00$$2NLM Chemicals$$aprotease-activated receptor 3
000014547 650_7 $$00$$2NLM Chemicals$$aprotease-activated receptor 4
000014547 650_7 $$050-99-7$$2NLM Chemicals$$aGlucose
000014547 650_7 $$07440-70-2$$2NLM Chemicals$$aCalcium
000014547 650_7 $$0EC 2.7.1.-$$2NLM Chemicals$$aprotein kinase C beta
000014547 650_7 $$0EC 2.7.11.13$$2NLM Chemicals$$aPRKCD protein, human
000014547 650_7 $$0EC 2.7.11.13$$2NLM Chemicals$$aProtein Kinase C
000014547 650_7 $$0EC 2.7.11.13$$2NLM Chemicals$$aProtein Kinase C-delta
000014547 650_7 $$0EC 3.4.21.5$$2NLM Chemicals$$aThrombin
000014547 650_7 $$2WoSType$$aJ
000014547 7001_ $$0P:(DE-HGF)0$$aRauch, B.H.$$b1
000014547 7001_ $$0P:(DE-Juel1)131924$$aGensch, T.$$b2$$uFZJ
000014547 7001_ $$0P:(DE-Juel1)VDB57287$$aDai, L.$$b3$$uFZJ
000014547 7001_ $$0P:(DE-HGF)0$$aBretschneider, E.$$b4
000014547 7001_ $$0P:(DE-HGF)0$$aVogelaar, C.F.$$b5
000014547 7001_ $$0P:(DE-HGF)0$$aSchrör, K.$$b6
000014547 7001_ $$0P:(DE-HGF)0$$aRosenkranz, A.C.$$b7
000014547 773__ $$0PERI:(DE-600)1494427-3$$a10.1161/ATVBAHA.110.219105$$gVol. 31, p. 624 - 633$$p624 - 633$$q31<624 - 633$$tArteriosclerosis, thrombosis, and vascular biology$$v31$$x1079-5642$$y2011
000014547 8567_ $$uhttp://dx.doi.org/10.1161/ATVBAHA.110.219105
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000014547 915__ $$0StatID:(DE-HGF)0020$$aNo peer review
000014547 9141_ $$y2011
000014547 9131_ $$0G:(DE-Juel1)FUEK505$$aDE-HGF$$bSchlüsseltechnologien$$kP45$$lBiologische Informationsverarbeitung$$vBioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung$$x0
000014547 9132_ $$0G:(DE-HGF)POF3-552$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bKey Technologies$$lBioSoft  Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vEngineering Cell Function$$x0
000014547 9201_ $$0I:(DE-Juel1)VDB922$$gISB$$kISB-1$$lZelluläre Biophysik$$x0
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