Background: Transforming growth factor (TGF)β is known to be a central player in the control of cardiac fibroblast properties and fibrosis. However, cellular and molecular mechanisms that trigger its activation remain poorly understood. Platelets are considered as a major source of TGFβ and recent evidence suggest that they are involved in TGFβ activation via Glycoprotein A Repetitions Predominant (GARP) present on their surface.

Aims: The present study sought to evaluate the role of platelet GARP in TGFβ activation using platelet specific GARP knockout mice.

Methods: We generated a new Cre transgenic mouse strain that allowed Megakaryocyte/platelet specific invalidation of GARP (GpIba-Cre x GARPfl/fl). The impact of GARP deficiency on platelet function was measured in vitro by flow cytometry using thrombin and CRP. Serum production of total and active TGFβ was assessed by ELISA.  

Results: Platelet count and other hematological parameters were normal in platelet specific GARP knockout mice, except platelet volume, which was increased by 10.3%, as compared to wild-type platelets. Stimulation by thrombin and CRP increased GARP exposure at platelet surface. However, platelets without GARP displayed normal agonist induced activation, as reflected by CD62P and αIIbβ3 exposure. Interestingly, the generation of active TGFβ was drastically impaired in the serum of platelet specific GARP knockout mice, while the amount of total TGFβ was not affected.

Conclusions: We provided evidence that platelet GARP is a crucial contributor to the systemic activation of TGFβ. Future work will aim to determine its role in cardiac fibroblast myodifferentiation and fibrosis.

« Back to ISTH 2021 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/role-of-platelet-garp-in-tgf%ce%b2-activation/