Abstract
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 P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 receptor in platelets in regulating ‘outside in’ integrin αIIbβ3 signalling thrombus growth and stability.
Original language | English |
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Pages (from-to) | 12-21 |
Number of pages | 10 |
Journal | Thrombosis Research |
Volume | 161 |
DOIs | |
Publication status | Published - 1 Jan 2018 |
Keywords
- Clopidogrel
- Mice
- Platelets
- Purinergic P2Y
- TSSC6