A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic P2Y12 receptor in platelets

Mohammed Makkawi, David Howells, Mark D. Wright, Denise E. Jackson

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

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 languageEnglish
Pages (from-to)12-21
Number of pages10
JournalThrombosis Research
Volume161
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Clopidogrel
  • Mice
  • Platelets
  • Purinergic P2Y
  • TSSC6

Cite this

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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.",
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A complementary role for tetraspanin superfamily member TSSC6 and ADP purinergic P2Y12 receptor in platelets. / Makkawi, Mohammed; Howells, David; Wright, Mark D.; Jackson, Denise E.

In: Thrombosis Research, Vol. 161, 01.01.2018, p. 12-21.

Research output: Contribution to journalArticleResearchpeer-review

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