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Desensitization of DMSO‐treated platelets to common agonists via membrane modulation (598.5)
Author(s) -
Yamaguchi Jonathan,
Tran Phat,
Sen Nivedita,
DeCook Tracy,
Slepian Marvin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.598.5
Subject(s) - platelet , chemistry , ristocetin , platelet activation , arachidonic acid , epinephrine , aspirin , desensitization (medicine) , pharmacology , platelet rich plasma , dimethyl sulfoxide , adenosine diphosphate , thrombin , biophysics , biochemistry , medicine , receptor , von willebrand factor , platelet aggregation , enzyme , biology , organic chemistry
Thrombosis and thromboembolic complications continue to plague mechanical circulatory support devices (MCS). Biochemical pathways involving prostaglandin and ADP are known targets for aspirin and thienopyridines to modulate platelet activation and aggregation, respectively. However, a recent study in our lab has demonstrated the limited ability of these agents to alter shear‐mediated platelet activation. Therefore, this study examines the impact of altering the platelet membrane fluidity by treatment with dimethyl sulfoxide (DMSO) and its inherent effects on platelet activation by standard agonists. DMSO was chosen due to its previously reported antithrombotic properties. Although it was reported that DMSO inhibits platelet activation through cyclooxygenase‐1 inhibition, we believe that the alteration in membrane fluidity also plays a key role in desensitization. Human venous blood was collected from healthy volunteers in citrated buffer with UA‐IRB consent. Platelet rich plasma (PRP) was isolated and treated with DMSO ranging from 0.95%‐60% (v/v). Light transmission aggregometry (LTA) was performed to detect platelet desensitization using arachidonic acid, ADP, collagen, epinephrine, and ristocetin. Platelets were fixed and visualized at the varying DMSO treatments under scanning electron microscopy (SEM). Collagen and epinephrine had limited effect on PRP aggregation ranging from 0.95% to 10% of DMSO. ADP and arachidonic acid showed a clear inhibition at 10% and 5%, respectively. DMSO had no effect on ristocetin‐induced platelet aggregation. SEM of platelets at 5% and 10% showed significant reduction in filopodia. DMSO altered platelet membrane fluidity and desensitized their aggregability from certain common agonists; thus reflecting the role of DMSO in some biochemical pathways that inhibit platelets. Next, we will measure the platelet membrane fluidity using TMA‐DPH and DPH fluorescence anisotropy in the presence of DMSO to further validate our results.