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Dipyridamole suppresses high glucose-induced osteopontin secretion and mRNA expression in rat aortic smooth muscle cells.

Authors: Hsieh, MS  Zhong, WB  Yu, SC  Lin, JY  Chi, WM  Lee, HM 
Citation: Hsieh MS, etal., Circ J. 2010 Jun;74(6):1242-50. Epub 2010 Apr 20.
Pubmed: (View Article at PubMed) PMID:20453393

BACKGROUND: Diabetic patients are frequently afflicted with medial artery calcification, a predictor of cardiovascular mortality. Diabetes induced the expression of osteopontin in arterial vasculature, which is an indicator of disease progression in artery calcification and vascular stiffness. Signal transduction and strategies that suppress high glucose-induced osteopontin expression in arterial vascular smooth muscle cells is investigated. METHODS AND RESULTS: The incubation of rat aortic smooth muscle cells under high glucose concentration increased osteopontin protein secretion and mRNA expression. Treatment with dipyridamole decreased high glucose-induced osteopontin expression and secretion. Dipyridamole decreased glucose-induced osteopontin through inhibition of phosphodiesterase, thereby increasing intracellular levels of adenosine-3',5'-cyclic monophosphate (cAMP) and guanosine-3',5'-cyclic monophosphate (cGMP), and increased thioredoxin expression to inhibit the reactive oxygen species (ROS) system. Induction of osteopontin was reversed when cells were pretreated with N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulfonamide (H89, cAMP-dependent protein kinase inhibitor), KT5823 (cGMP-dependent protein kinase inhibitor), or dinitrochlorobenzene (thioredoxin reductase inhibitor). The antioxidant, N-acetyl-L-cysteine, suppressed glucose-induced osteopontin expression by decreasing ROS concentration. Both H89 and KT5823 downregulated thioredoxin expression. CONCLUSIONS: These results suggest a novel effect for dipyridamole to suppress high glucose-induced osteopontin protein secretion and mRNA expression. Dipyridamole has antioxidant properties and a phosphodiesterase inhibitor activity, which might be useful to ameliorate diabetic vasculopathy and its cardiovascular complications.


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CRRD Object Information
CRRD ID: 5133719
Created: 2011-06-28
Species: All species
Last Modified: 2011-06-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.