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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.

Deep venous thrombosis (DVT) of the upper extremity is an unusual thrombotic event (1-2% of all DVT) which can be conveniently divided into two categories, traumatic (including "stress") and spontaneous. The spontaneous form is not reported as often in the literature, but occurs more commonly than the traumatic form. There is an increased left-sided predominance in spontaneous DVT compared with the traumatic form, where a right-sided predominance exists. Possible anatomical and physiological explanations are offered for the left-sided predominance in spontaneous DVT of the upper extremity. The thrombogenesis of DVT of the upper extremity is compared with DVT of the lower extremity. An analysis of responses to therapy and considerations for other therapeutic approaches are offered.

Primary cultures of confluent endothelial cells derived from human umbilical veins produce platelet-activating factor (PAF) (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with appropriate agonists. Highly purified human thrombin and calcium ionophore A23187 stimulate the incorporation of [3H] acetate into a lipid product that has been identified as PAF by its behavior in thin-layer chromatographic and high-performance liquid chromatographic systems, the presence of characteristic biologic activity, and appropriate response to phospholipases. A number of other humoral mediators, examined because they directly influence the activity of vascular cells or because they may mediate endothelial injury, do not stimulate PAF production by endothelial cells. This indicates that the synthesis of PAF by cultured human endothelial cells is a response to specific agonists and is not an unregulated event that occurs as a result of nonspecific cellular perturbation. The PAF produced by thrombin-treated endothelial cells is a potent stimulus for platelet activation, as assayed by the aggregation of human platelets in autologous plasma. The production of PAF by endothelial monolayers is attenuated by prostacyclin, another product of stimulated endothelial cells. Conversely, PAF production is enhanced by treatment of the endothelial cells with indomethacin, an inhibitor of prostacyclin synthesis from arachidonic acid, indicating that endogenously generated prostacyclin may modulate PAF synthesis. The potential to synthesize PAF, a unique lipid autocoid that stimulates the activation of both platelets and polymorphonuclear leukocytes, suggests that endothelial cells can directly influence the activity of these circulating effector cells. This biologic potential may be important in the interaction of the endothelium with circulating blood cells in physiologic conditions and in syndromes of vascular injury.