DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?
BACKGROUND
DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents.


RESULTS
Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54+/-0.9427%, n=5, P<0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0%+/-4.031, n=9, P=0.0004 versus control) as well as a decreased maximal aggregation (-6.388+/-2.212%, n=6, P=0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition.


CONCLUSIONS
Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents.
Asmis
Lars
L
Institute for Clinical Hematology, University Hospital Zürich, Zürich, Switzerland.
Tanner
Felix C
FC
Sudano
Isabella
I
Lüscher
Thomas F
TF
Camici
Giovanni G
GG
D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control
D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D004121:Dimethyl Sulfoxide