Premium
Inhibition of Nuclear Factor of Activated T‐cells (NFAT) reduces diabetes‐induced atherosclerosis
Author(s) -
Zetterqvist Anna V,
Berglund Lisa M,
Wigren Maria,
To Fong,
Nilsson Jan,
Bengtsson Eva,
Gomez Maria F
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1028.7
Subject(s) - nfat , medicine , endocrinology , diabetes mellitus , osteopontin , calcineurin , transplantation
Macrovascular complications of diabetes include myocardial infarction, stroke and peripheral vascular disease. The molecular mechanism underlying vascular damage is still unclear. We recently showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, leading to increased expression of the pro‐atherosclerotic protein osteopontin (OPN). Here we tested if NFAT is involved in the development of macroangiopathy. Four weeks after induction of diabetes with streptozotocin, ApoE KO mice had a 2.2 fold increased aortic atherosclerosis, enhanced OPN expression in subvalvular aortic lesions and increased plasma OPN. In vivo treatment with the NFAT blocker A‐285222 completely inhibited the hyperglycemia‐induced aggravation of atherosclerosis, without affecting non‐diabetic mice. Diabetes also resulted in elevated plasma cholesterol, triglycerides and IL‐6, IFN‐γ, IL‐12p70, IL‐1β, IL‐10 and TNFα, but only IL‐6 was significantly reduced by A‐285222. NFAT‐dependent transcriptional activity in spleen and thymus and splenocyte proliferation rate were unaffected by A‐285222 treatment. Together these data suggest that the reduced atherosclerosis is less likely due to a lipid lowering effect or systemic immunosuppression. We provide evidence for the involvement of NFAT in the development of diabetic macroangiopathy. Support: Swedish Res Council/Heart & Lung Foundation.