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Thromb Haemost 2017; 117(09): 1782-1797
DOI: 10.1160/TH17-02-0112
Cellular Haemostasis and Platelets
Schattauer GmbH

Absence of transforming growth factor beta 1 in murine platelets reduces neointima formation without affecting arterial thrombosis

Eva Schütz
1   Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany
3   Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany
,
Magdalena L. Bochenek
1   Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany
2   Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
3   Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany
,
Dennis R. Riehl
2   Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
,
Markus Bosmann
2   Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
3   Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany
,
Thomas Münzel
1   Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany
3   Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany
,
Stavros Konstantinides
2   Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany
3   Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany
,
Katrin Schäfer
1   Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany
3   Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany
› Author Affiliations
Further Information

Publication History

Received: 17 February 2017

Accepted after major revision: 11 June 2017

Publication Date:
28 November 2017 (online)

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Summary

Platelet degranulation at the site of vascular injury prevents bleeding and may affect the chronic vascular wound healing response. Transforming Growth Factor (TGF)-β1 is a major component of platelet α-granules known to accumulating in thrombi. It was our aim to determine the role of TGFβ1 released from activated platelets for neointima formation following arterial injury and thrombosis. Mice with platelet-specific deletion of TGFβ1 (Plt.TGFβ-KO) underwent carotid artery injury. Immunoassays confirmed the absence of active TGFβ1 in platelet releasates and plasma of Plt.TGFβ-KO mice. Whole blood analyses revealed similar haematological parameters, and tail cut assays excluded major bleeding defects. Platelet aggregation and the acute thrombotic response to injury in vivo did not differ between Plt.TGFβ-KO and Plt.TGFβ-WT mice. Morphometric analysis revealed that absence of TGFβ1 in platelets resulted in a significant reduction of neointima formation with lower neointima area, intima-to-media ratio, and lumen stenosis. On the other hand, the media area was enlarged in mice lacking TGFβ1 in platelets and contained increased amounts of proteases involved in latent TGFβ activation, including MMP2, MMP9 and thrombin. Significantly increased numbers of proliferating cells and cells expressing the mesenchymal markers platelet-derived growth factor receptor-β or fibroblast-specific protein-1, and the macrophage antigen F4/80, were observed in the media of Plt.TGFβ-KO mice, whereas the medial smooth muscle-actin-immuno-positive area and collagen content did not differ between genotypes. Our findings support an essential role for platelet-derived TGFβ1 for the vascular remodelling response to arterial injury, apparently independent from the role of platelets in thrombosis or haemostasis.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Neointima - platelets - thrombosis - transforming growth factor beta 1 - vascular injury

 

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