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

Berglund, Lisa (author)
Lund 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
Zetterqvist, Anna (author)
Lund 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
Öhman, Jenny (author)
Lund 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
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Sigvardsson, Mikael (author)
Lund 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
Gonzalez Bosc, Laura V (author)
Department of Cell Biology & Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA
Smith, Maj-Lis (author)
Lund 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
Salehi, S Albert (author)
Lund University,Lunds universitet,Islet cell physiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Department of Clinical Sciences in Malmö, Lund University, Malmö
Agardh, Elisabet (author)
Lund 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
Nordin Fredrikson, Gunilla (author)
Lund 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
Agardh, Carl-David (author)
Lund 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
Nilsson, Jan (author)
Lund 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
Wamhoff, Brian R. (author)
Department of Medicine, University of Virginia, Charlottesville, VA, USA
Hultgårdh, Anna (author)
Lund University,Lunds universitet,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Vessel Wall Biology,Lund University Research Groups,Department of Experimental Medical Science, Lund University, Lund
Gomez, Maria (author)
Lund 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
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 (creator_code:org_t)
Baltimore : Lippincott Williams & Wilkins, 2010
2010
English.
In: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY. - Baltimore : Lippincott Williams & Wilkins. - 1079-5642. ; 30, s. 154-218
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

NFAT
diabetes
hyperglycemia
UTP
vascular complications
inflammation
MEDICINE
MEDICIN

Publication and Content Type

ref (subject category)
art (subject category)

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