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

Ming-Song Hsieh, Wen Bin Zhong, Shu Chuan Yu, John Yi Chuan Lin, Wei Ming Chi, Horng Mo Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 pre-treated 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 osteopon-tin 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.

Original languageEnglish
Pages (from-to)1242-1250
Number of pages9
JournalCirculation Journal
Volume74
Issue number6
DOIs
Publication statusPublished - 2010

Fingerprint

Osteopontin
Dipyridamole
Smooth Muscle Myocytes
Glucose
Messenger RNA
Thioredoxins
Cyclic GMP
Protein Kinase Inhibitors
Reactive Oxygen Species
Arteries
Antioxidants
Thioredoxin-Disulfide Reductase
Dinitrochlorobenzene
Vascular Stiffness
Phosphodiesterase Inhibitors
Tin
Phosphoric Diester Hydrolases
Acetylcysteine
Cyclic AMP-Dependent Protein Kinases
Vascular Smooth Muscle

Keywords

  • Diabetes mellitus
  • Dipyridamole
  • High glucose
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Dipyridamole suppresses high glucose-induced osteopontin secretion and mRNA expression in rat aortic smooth muscle cells. / Hsieh, Ming-Song; Zhong, Wen Bin; Yu, Shu Chuan; Lin, John Yi Chuan; Chi, Wei Ming; Lee, Horng Mo.

In: Circulation Journal, Vol. 74, No. 6, 2010, p. 1242-1250.

Research output: Contribution to journalArticle

Hsieh, Ming-Song ; Zhong, Wen Bin ; Yu, Shu Chuan ; Lin, John Yi Chuan ; Chi, Wei Ming ; Lee, Horng Mo. / Dipyridamole suppresses high glucose-induced osteopontin secretion and mRNA expression in rat aortic smooth muscle cells. In: Circulation Journal. 2010 ; Vol. 74, No. 6. pp. 1242-1250.
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AU - Hsieh, Ming-Song

AU - Zhong, Wen Bin

AU - Yu, Shu Chuan

AU - Lin, John Yi Chuan

AU - Chi, Wei Ming

AU - Lee, Horng Mo

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N2 - 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 pre-treated 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 osteopon-tin 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.

AB - 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 pre-treated 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 osteopon-tin 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.

KW - Diabetes mellitus

KW - Dipyridamole

KW - High glucose

KW - Signal transduction

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