Journal
THROMBOSIS RESEARCH
Volume 161, Issue -, Pages 12-21Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2017.11.009
Keywords
Platelets; TSSC6; Mice; Clopidogrel; Purinergic P2Y12
Categories
Funding
- NHF of Australia [G09M 4360]
- NHMRC of Australia [603812]
- King Khalid University in Saudi Arabia
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Tumor-suppressing subchromosomal transferable fragment cDNA 6 (TSSC6) expression is restricted to hematopoietic organs and tissues where it plays a role in hematopoietic-cell function. The ADP purinergic receptor P2Y(12) is mainly expressed by platelets with important clinical significance as a target for several clinically approved antithrombotic agents. We have previously shown a physical association between P2Y(12) and TSSC6 in platelets. Hence our aim was to investigate whether this physical association is translated to functional effects. To investigate this possibility, we used wild-type or TSSC6 knockout (KO) mice treated with either PBS or 50 mg/kg clopidogrel. TSSC6 KO mice treated with clopidogrel exhibited synergy in delayed kinetics of clot retraction, reduced collagen-mediated platelet aggregation, and platelet spreading on fibrinogen. Platelets derived from TSSC6 mice with P2Y(12) blockade form smaller thrombi when perfused over a collagen matrix under arterial flow. Clopidogrel treated TSSC6 KO arterioles showed smaller and less stable thrombi with increased tendency to embolise in vivo. These studies demonstrate a complementary role between TSSC6 and P2Y(12) receptor in platelets in regulating ` outside in' integrin aIIb beta 3 signalling thrombus growth and stability.
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