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

Keywords

  • Diabetes mellitus
  • Dipyridamole
  • High glucose
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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