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

Eva Schütz; Magdalena L. Bochenek; Dennis R. Riehl; Markus Bosmann; Thomas Münzel; Stavros Konstantinides; Katrin Schäfer

doi:10.1160/TH17-02-0112

Thrombosis and Haemostasis, Table of Contents

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

¹Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany

³Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany

,

Magdalena L. Bochenek

¹Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany

²Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

³Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany

,

Dennis R. Riehl

²Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

,

Markus Bosmann

²Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

³Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany

,

Thomas Münzel

¹Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany

³Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany

,

Stavros Konstantinides

²Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

³Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany

,

Katrin Schäfer

¹Center for Cardiology, Cardiology I, University Medical Center Mainz, Mainz, Germany

³Center for Translational Vascular Biology (CTVB), University Medical Center Mainz, Mainz, Germany

› Author Affiliations

Abstract

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

Full Text

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