Document Detail


Dipyridamole suppresses high glucose-induced osteopontin secretion and mRNA expression in rat aortic smooth muscle cells.
MedLine Citation:
PMID:  20453393     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ming-Song Hsieh; Wen-Bin Zhong; Shu-Chuan Yu; John Yi-Chung Lin; Wei-Ming Chi; Horng-Mo Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-20
Journal Detail:
Title:  Circulation journal : official journal of the Japanese Circulation Society     Volume:  74     ISSN:  1347-4820     ISO Abbreviation:  Circ. J.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-27     Completed Date:  2010-09-07     Revised Date:  2011-02-18    
Medline Journal Info:
Nlm Unique ID:  101137683     Medline TA:  Circ J     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  1242-50     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Shuang-Ho Hospital, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants
Aorta / cytology*
Biological Markers / analysis
Calcinosis
Cells, Cultured
Diabetic Angiopathies
Dipyridamole / pharmacology*
Glucose / pharmacology*
Humans
Muscle, Smooth, Vascular / secretion*
Myocytes, Smooth Muscle / cytology,  secretion
Osteopontin / analysis,  metabolism,  secretion*
Phosphodiesterase Inhibitors
RNA, Messenger / analysis*
Rats
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Biological Markers; 0/Phosphodiesterase Inhibitors; 0/RNA, Messenger; 0/Reactive Oxygen Species; 106441-73-0/Osteopontin; 50-99-7/Glucose; 58-32-2/Dipyridamole

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