liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Nuclear Factor of Activated T Cells Regulates Osteopontin Expression in Arterial Smooth Muscle in Response to Diabetes-Induced Hyperglycemia
Department of Clinical Sciences in Malmö, Lund University, Malmö.
Department of Clinical Sciences in Malmö, Lund University, Malmö.
Department of Clinical Sciences in Malmö, Lund University, Malmö.
Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology. Linköping University, Faculty of Health Sciences.
Show others and affiliations
2010 (English)In: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, ISSN 1079-5642, Vol. 30, no 2, 218-224 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Baltimore: Lippincott Williams & Wilkins, 2010. Vol. 30, no 2, 218-224 p.
Keyword [en]
NFAT, diabetes, hyperglycemia, UTP, vascular complications, inflammation
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-53840DOI: 10.1161/ATVBAHA.109.199299ISI: 000273799900017OAI: diva2:292194
Available from: 2010-02-05 Created: 2010-02-05 Last updated: 2012-01-27

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Sigvardsson, Mikael
By organisation
Experimental HematologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 30 hits
ReferencesLink to record
Permanent link

Direct link