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Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates.

Abstract：

BACKGROUND:Drugs that simultaneously decrease platelet function and inflammation may improve the treatment of cardiovascular disorders. Here, we determined whether dipyridamole and aspirin, a combination therapy used to prevent recurrent stroke, regulates gene expression in platelet-monocyte inflammatory model systems. METHODS AND RESULTS:Human platelets and monocytes were pretreated with dipyridamole, aspirin, or both inhibitors. The cells were stimulated with thrombin or activated by adhesion to collagen, and gene expression was measured in the target monocytes. Thrombin-stimulated platelets increased monocyte chemotactic protein-1 (MCP-1) expression by monocytes. Dipyridamole but not aspirin attenuated nuclear translocation of NF-kappaB and blocked the synthesis of MCP-1 at the transcriptional level. Dipyridamole delayed maximal synthesis of interleukin-8 but did not alter cyclooxygenase-2 accumulation. Adherence to collagen and platelets also increased the expression of matrix metalloproteinase-9 (MMP-9) in monocytes, a response that was inhibited by dipyridamole. In this case, however, dipyridamole did not block transcription or distribution of MMP-9 mRNA to actively translating polysomes, indicating that it regulates the expression of MMP-9 protein at a postinitiation stage of translation. Dipyridamole also blocked MCP-1 and MMP-9 generated by lipopolysaccharide-treated monocytes, indicating that at least part of its inhibitory action is unrelated to its antiplatelet properties. CONCLUSIONS:These results indicate that dipyridamole has selective antiinflammatory properties that may contribute to its actions in the secondary prevention of stroke.

journal_name

Circulation

journal_title

Circulation

authors

Weyrich AS,Denis MM,Kuhlmann-Eyre JR,Spencer ED,Dixon DA,Marathe GK,McIntyre TM,Zimmerman GA,Prescott SM

doi

10.1161/01.CIR.0000154607.90506.45

subject

Has Abstract

pub_date

2005-02-08 00:00:00

pages

633-42

issue

5

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000154607.90506.45

journal_volume

111

pub_type

杂志文章

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