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<p>Platelets bind plasminogen facilitating surface-bound plasmin generation. We previously reported that the plasminogen receptor, Plg-R<sub>KT</sub>, retains plasminogen on activated platelets. Here, we investigate the significance of the interaction of Plg-R<sub>KT</sub> on thrombus formation, growth and stability. Whole blood from Plg-R<sub>KT</sub><sup>−/−</sup> or littermate Plg-R<sub>KT</sub><sup>+/+</sup> mice was flowed over collagen/tissue factor-coated microfluidic biochips at 250 or 1000&#xa0;s<sup>−1</sup> to reflect venous and arterial shear rates. AlexaFluor488-fibrinogen and Dylight633-labelled-plasminogen accumulation was monitored in real-time by fluorescence microscopy in the presence or absence of tissue plasminogen activator (tPA). At 1000&#xa0;s<sup>−1</sup>, plasminogen accumulation was reduced in thrombi formed from Plg-R<sub>KT</sub><sup>−/−</sup> mice compared to Plg-R<sub>KT</sub><sup>+/+</sup> mice. Fibrin(ogen) accumulation in Plg-R<sub>KT</sub><sup>−/−</sup> mice persisted for the duration of the experiment, indicating impaired fibrinolysis compared to Plg-R<sub>KT</sub><sup>+/+</sup> mice. Mice were subjected to FeCl<sub>3</sub> carotid artery model of thrombosis followed by tPA infusion. Initial platelet deposition was faster in Plg-R<sub>KT</sub><sup>−/−</sup> mice compared to Plg-R<sub>KT</sub><sup>+/+</sup> mice. Fibrin(ogen) accumulation and persistence was enhanced in Plg-R<sub>KT</sub><sup>−/−</sup> mice indicating impaired fibrinolysis. We demonstrate for the first time that under arterial shear, Plg-R<sub>KT</sub> facilitates plasminogen incorporation and limits both platelet recruitment to the forming thrombus and fibrin accumulation. These data highlight that Plg-R<sub>KT</sub> and potentially plasmin on the platelet surface regulate arterial thrombus growth.</p>

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Plg-RKT facilitates plasminogen incorporation and restrains thrombus growth under arterial shear in mice

  • 期刊论文

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  • 发表日期：

    2026年5月13日

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  • Claire S. Whyte,
  • Dean Kavanagh,
  • Ausra S. Lionikiene,
  • Steve P. Watson,
  • Robert J. Parmer,
  • Lindsey A. Miles,
  • Nicola J. Mutch

摘要

Platelets bind plasminogen facilitating surface-bound plasmin generation. We previously reported that the plasminogen receptor, Plg-RKT, retains plasminogen on activated platelets. Here, we investigate the significance of the interaction of Plg-RKT on thrombus formation, growth and stability. Whole blood from Plg-RKT−/− or littermate Plg-RKT+/+ mice was flowed over collagen/tissue factor-coated microfluidic biochips at 250 or 1000 s−1 to reflect venous and arterial shear rates. AlexaFluor488-fibrinogen and Dylight633-labelled-plasminogen accumulation was monitored in real-time by fluorescence microscopy in the presence or absence of tissue plasminogen activator (tPA). At 1000 s−1, plasminogen accumulation was reduced in thrombi formed from Plg-RKT−/− mice compared to Plg-RKT+/+ mice. Fibrin(ogen) accumulation in Plg-RKT−/− mice persisted for the duration of the experiment, indicating impaired fibrinolysis compared to Plg-RKT+/+ mice. Mice were subjected to FeCl3 carotid artery model of thrombosis followed by tPA infusion. Initial platelet deposition was faster in Plg-RKT−/− mice compared to Plg-RKT+/+ mice. Fibrin(ogen) accumulation and persistence was enhanced in Plg-RKT−/− mice indicating impaired fibrinolysis. We demonstrate for the first time that under arterial shear, Plg-RKT facilitates plasminogen incorporation and limits both platelet recruitment to the forming thrombus and fibrin accumulation. These data highlight that Plg-RKT and potentially plasmin on the platelet surface regulate arterial thrombus growth.