Dipyridamole Selectively Inhibits Inflammatory Gene Expression in Platelet–Monocyte Aggregates
- 8 February 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 111 (5), 633-642
- https://doi.org/10.1161/01.cir.0000154607.90506.45
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-κB 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.Keywords
This publication has 32 references indexed in Scilit:
- Rapid platelet inhibition after a single capsule of Aggrenox®: Challenging a conventional full‐dose aspirin antiplatelet advantage?American Journal of Hematology, 2003
- Dipyridamole Enhances NO/cGMP-Mediated Vasodilator-Stimulated Phosphoprotein Phosphorylation and Signaling in Human PlateletsStroke, 2003
- Inflammation in atherosclerosisNature, 2002
- A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion FormationThe Journal of Experimental Medicine, 2002
- Inhibition of Cytokine-induced Matrix Metalloproteinase 9 Expression by Peroxisome Proliferator-activated Receptor α Agonists Is Indirect and Due to a NO-mediated Reduction of mRNA StabilityJournal of Biological Chemistry, 2002
- Suppression of granulocyte/macrophage colony‐stimulating factor release from human monocytes by cyclic AMP‐elevating drugs: role of interleukin‐10British Journal of Pharmacology, 2001
- Activated platelets mediate inflammatory signaling by regulated interleukin 1β synthesisThe Journal of cell biology, 2001
- Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking.JCI Insight, 1997
- Activated platelets signal chemokine synthesis by human monocytes.JCI Insight, 1996
- Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation.JCI Insight, 1995