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BMC Pharmacology and Toxicology

Open Access

Real-time imaging of cGMP signals in platelets

  • Lai Wen1Email author,
  • Martin Thunemann1,
  • Kjestine Schmidt2,
  • Cor de Wit2,
  • Susanne Feil1,
  • Marcus Olbrich3,
  • Harald Langer3,
  • Meinrad Gawaz3 and
  • Robert Feil1
BMC Pharmacology and Toxicology201516(Suppl 1):A98

Published: 2 September 2015


cGMP plays an essential role in platelet aggregation. However, the intracellular cGMP concentrations and the spatiotemporal dynamics of cGMP signals in platelets during hemostasis and thrombosis are largely unknown. To visualize cGMP signals in vivo, we have generated so-called cGMP sensor knock-in mice [1]. A Cre recombinase-activatable expression cassette encoding the fluorescence resonance energy transfer (FRET)-based cGMP sensor, cGi500, driven by the CAG promoter was integrated into the Rosa26 locus. Depending on the strategy to activate sensor expression, these mice can show either ubiquitous or tissue-specific sensor expression allowing for delineation of cGMP signaling in live cells in vitro and in vivo.


cGMP signaling was dissected through real-time FRET imaging of activated mouse platelet thrombi in vitro in a flow chamber system. We found that NO triggers fast cGMP signals in platelet thrombi under flow, and that PDE2, 3 and 5 are responsible for cGMP degradation. Simultaneous imaging of cGMP and Ca2+ revealed that the concentration of these two second messengers has an inverse relationship. NO-induced cGMP signals suppress procoagulant Ca2+ signals, indicating an inhibitory effect of cGMP on platelet aggregation under these conditions. Moreover, using a mouse model of mechanical injury-induced thrombosis in the arterioles of the cremaster muscle, intravital FRET imaging showed that endogenous cGMP signals in platelets increase robustly during thrombus growth in vivo.


Taken together, our data demonstrate that the cGMP sensor knock-in mice are useful tools for real-time monitoring of cGMP signals in platelets. cGMP may act as a brake to prevent the platelet thrombus from overgrowth and vessel occlusion via cGMP/Ca2+ signaling.

Authors’ Affiliations

Interfakultäres Institut für Biochemie, University of Tübingen
Institut für Physiologie, Universität zu Lübeck
Department of Cardiology & Cardiovascular Medicine, University of Tübingen


  1. Thunemann M, Wen L, et al: Transgenic mice for cGMP imaging. Circ Res. 2013, 113 (4): 365-371. 10.1161/CIRCRESAHA.113.301063.View ArticlePubMedPubMed CentralGoogle Scholar


© Wen et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.