Dimethyl fumarate possesses antiplatelet and antithrombotic properties

Background: Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has been approved for treating multiple sclerosis (MS) and psoriasis due to anti-inflammatory effect. There is a close association between platelets and the pathogenesis of MS. Whether DMF affects platelet function remains unclear. Our study intends to evaluate DMF's effect on platelet function. Methods: Washed human platelets were treated with different concentrations of DMF (0, 50, 100 and 200 & mu;M) at 37 degrees C for 1 h followed by analysis of platelet aggregation, granules release, receptors expression, spreading and clot retraction. In addition, mice received intraperitoneal injection of DMF (15 mg/kg) to assess tail bleeding time, arterial and venous thrombosis. Results: DMF significantly inhibited platelet aggregation and the release of dense/alpha granules in response to collagen-related peptide (CRP) or thrombin stimulation dose-dependently without altering the expression of platelet receptors & alpha;IIb & beta;3, GPIb & alpha;, and GPVI. In addition, DMF-treated platelets presented significantly reduced spreading on collagen or fibrinogen and thrombin-mediated clot retraction along with the decreased phosphorylation of c-Src and PLC & gamma;2. Moreover, administration of DMF into mice significantly prolonged the tail bleeding time and impaired arterial and venous thrombus formation. Furthermore, DMF reduced the generation of intracellular reactive oxygen species and calcium mobilization, and inhibited NF-& kappa;B activation and the phosphorylation of ERK1/2, p38 and AKT. Conclusion: DMF inhibits platelet function and arterial/venous thrombus formation. Considering the presence of thrombotic events in MS, our study indicates that DMF treatment for patients with MS might obtain both antiinflammatory and anti-thrombotic benefits.

Automated summary

This study aimed to evaluate the effect of Dimethyl fumarate (DMF) on platelet function. The results showed that DMF significantly inhibited platelet aggregation and granule release, reduced platelet spreading and clot retraction, and prolonged bleeding time in mice. Furthermore, DMF also reduced the generation of reactive oxygen species and inhibited NF-κB activation and phosphorylation of ERK1/2, p38 and AKT. Overall, DMF inhibits platelet function and thrombus formation.