gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Intracellular calcium is essential for stable thrombus formation – the role of STIM1

Meeting Abstract

Suche in Medline nach

  • David Varga-Szabo - Helios Klinikum Wuppertal, Chirurgisches Zentrum, Wuppertal
  • Hubert Zirngibl - Helios Klinikum Wuppertal, Chirurgisches Zentrum, Wuppertal
  • Bernhard Nieswandt - Rudolf Virchow Center, Experimentelle Biomedizin - Vaskuläre Medizin, Würzburg

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch817

DOI: 10.3205/11dgch817, URN: urn:nbn:de:0183-11dgch8170

Veröffentlicht: 20. Mai 2011

© 2011 Varga-Szabo et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Myocardial infarction and stroke are two of the leading causes of mortality and with the worldwide growing life expectations more and more patients with cardio- and cerebrovascular diseases and with the need of lifetime anticoagulation undergo surgery. All antithrombotics available at present have, however, the major side effect of increasing bleeding risk - especially important in the case of surgery. Therefore, a better understanding of platelet function and thrombus formation is required in order to develop new antithrombotics.

Intracellular calcium is known to be of pivotal importance for platelet activation. Its role in thrombus formation in vivo, however, is unclear. Stromal interaction molecule 1 (STIM1) is a calcium sensor in the major intracellular calcium store, the endoplasmic reticulum (ER). Upon calcium release from the ER, a central event in platelet activation, it opens the calcium channels in the plasma membrane, thereby further increasing the intracellular calcium concentration.

Materials and methods: Using knock-out mice intracellular calcium measurements were performed. Further using a tail bleeding time assay and a chemical injury in vivo thrombosis model of mesenteric arteries, we have investigated the role of STIM1 and calcium in thrombus formation.

Results: Platelets lacking STIM1 show ~90% reduced calcium entry following platelet activation. This results in severely defective thrombus formation in vivo (8 of 10 arteries occluded in wild-type mice vs. 9 of 10 arteries remained open in knockout mice) with only minor influence on bleeding time (28 of 30 wild-type mice vs. 20 of 31 knockout mice stop bleeding within 10 minutes).

Conclusion: In conclusion we can say that STIM1 is the main regulator of calcium influx in platelets and this process is essential for stable thrombus formation in vivo. Importantly, the residual platelet function seems to be sufficient to limit posttraumatic bleeding. Therefore, STIM1 is a potential target for the development of new antithrombotics.