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  • Berglund, LisaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö (author)

Nuclear Factor of Activated T Cells Regulates Osteopontin Expression in Arterial Smooth Muscle in Response to Diabetes-Induced Hyperglycemia

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • Baltimore :Lippincott Williams & Wilkins,2010
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-53840
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-53840URI
  • https://doi.org/10.1161/ATVBAHA.109.199299DOI
  • https://lup.lub.lu.se/record/1523873URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Objective-Hyperglycemia is a recognized risk factor for cardiovascular disease in diabetes. Recently, we reported that high glucose activates the Ca2+/calcineurin-dependent transcription factor nuclear factor of activated T cells (NFAT) in arteries ex vivo. Here, we sought to determine whether hyperglycemia activates NFAT in vivo and whether this leads to vascular complications. Methods and Results-An intraperitoneal glucose-tolerance test in mice increased NFATc3 nuclear accumulation in vascular smooth muscle. Streptozotocin-induced diabetes resulted in increased NFATc3 transcriptional activity in arteries of NFAT-luciferase transgenic mice. Two NFAT-responsive sequences in the osteopontin (OPN) promoter were identified. This proinflammatory cytokine has been shown to exacerbate atherosclerosis and restenosis. Activation of NFAT resulted in increased OPN mRNA and protein in native arteries. Glucose-induced OPN expression was prevented by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. The calcineurin inhibitor cyclosporin A or the novel NFAT blocker A-285222 prevented glucose-induced OPN expression. Furthermore, diabetes resulted in higher OPN expression, which was significantly decreased by in vivo treatment with A-285222 for 4 weeks or prevented in arteries from NFATc3(-/-) mice. Conclusions-These results identify a glucose-sensitive transcription pathway in vivo, revealing a novel molecular mechanism that may underlie vascular complications of diabetes.

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  • Zetterqvist, AnnaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)med-aaz (author)
  • Öhman, JennyLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)mphy-jni (author)
  • Sigvardsson, MikaelLund University,Lunds universitet,Linköpings universitet,Experimentell hematologi,Hälsouniversitetet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)stem-msi (author)
  • Gonzalez Bosc, Laura VDepartment of Cell Biology & Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA (author)
  • Smith, Maj-LisLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)efor-msm (author)
  • Salehi, S AlbertLund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)farm-sal (author)
  • Agardh, ElisabetLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)ofta-eag (author)
  • Nordin Fredrikson, GunillaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)medf-gno (author)
  • Agardh, Carl-DavidLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)endo-cag (author)
  • Nilsson, JanLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)medf-jni (author)
  • Wamhoff, Brian R.Department of Medicine, University of Virginia, Charlottesville, VA, USA (author)
  • Hultgårdh, AnnaLund University,Lunds universitet,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Vessel Wall Biology,Lund University Research Groups,Department of Experimental Medical Science, Lund University, Lund(Swepub:lu)medk-ahu (author)
  • Gomez, MariaLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö(Swepub:lu)mphy-mgo (author)
  • Kardiovaskulär forskning - immunitet och aterosklerosForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGYBaltimore : Lippincott Williams & Wilkins30, s. 154-2181079-5642
  • In:Arteriosclerosis, Thrombosis and Vascular BiologyBaltimore : Lippincott Williams & Wilkins30, s. 154-2181524-4636

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