Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura.

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  • Additional Information
    • Publication Year:
      2016
    • Author-Supplied Keywords:
      ADAMTS ‐ 13 protein
      ADAMTS-13 protein
      endothelium
      myocardial ischemia
      oxidative stress
      thrombotic thrombocytopenic purpura
    • NAICS/Industry Codes:
      NAICS/Industry Codes 621512 Diagnostic Imaging Centers
      112990 All Other Animal Production
    • Abstract:
      Background Cardiac alterations represent a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). Endothelial injury remains poorly defined, but seems to be a key initiating event leading to the formation of platelet-rich thrombi in TTP patients. Objectives To assess the changes in endothelial function and the induced cardiac damage in a mouse model of TTP. Patients/methods We used an animal model in which TTP-like symptoms are triggered by injection of 2000 units kg−1 of recombinant von Willebrand factor in ADAMTS-13 knockout mice. Results These mice developed TTP-like symptoms, i.e. severe thrombocytopenia, schistocytosis, and anemia. On day 2, magnetic resonance imaging demonstrated a decrease in left ventricular perfusion associated with alteration of left ventricular ejection fraction, fractional shortening, and cardiac output, suggesting early systolic dysfunction. This was associated with decrease in endothelium-mediated relaxation responses to acetylcholine in mesenteric and coronary arteries, demonstrating severe early endothelial dysfunction. In parallel, we showed decreased cardiac expression of endothelial nitric oxide (NO) synthase and increased expression of antioxidant enzymes, suggesting alteration of the NO pathway. At this time, cardiac immunohistochemistry revealed an increase in the expression of VCAM-1 and E-selectin. Conclusion This study provides evidence that the heart is a sensitive target organ in TTP, and shows, for the first time, strong mesenteric and coronary endothelial dysfunction in an induced-TTP model. The mechanisms incriminated are the occurrence of a pro-oxidant state, and proadhesive and proinflammatory phenotypes. This previously largely unrecognized vascular dysfunction may represent an important contributor to the systemic organ failure occurring in TTP. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of Journal of Thrombosis & Haemostasis is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
    • ISSN:
      15387933
    • Accession Number:
      119103082
  • Citations
    • ABNT:
      LE BESNERAIS, M. et al. Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura. Journal of Thrombosis & Haemostasis, [s. l.], v. 14, n. 10, p. 1917, 2016. Disponível em: . Acesso em: 24 ago. 2019.
    • AMA:
      Le Besnerais M, Favre J, Denis CV, et al. Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura. Journal of Thrombosis & Haemostasis. 2016;14(10):1917. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082. Accessed August 24, 2019.
    • APA:
      Le Besnerais, M., Favre, J., Denis, C. V., Mulder, P., Martinet, J., Nicol, L., … Benhamou, Y. (2016). Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura. Journal of Thrombosis & Haemostasis, 14(10), 1917. Retrieved from http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082
    • Chicago/Turabian: Author-Date:
      Le Besnerais, M., J. Favre, C. V. Denis, P. Mulder, J. Martinet, L. Nicol, H. Levesque, et al. 2016. “Assessment of Endothelial Damage and Cardiac Injury in a Mouse Model Mimicking Thrombotic Thrombocytopenic Purpura.” Journal of Thrombosis & Haemostasis 14 (10): 1917. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082.
    • Harvard:
      Le Besnerais, M. et al. (2016) ‘Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura’, Journal of Thrombosis & Haemostasis, 14(10), p. 1917. Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082 (Accessed: 24 August 2019).
    • Harvard: Australian:
      Le Besnerais, M, Favre, J, Denis, CV, Mulder, P, Martinet, J, Nicol, L, Levesque, H, Veyradier, A, Kopić, A, Motto, DG, Coppo, P, Richard, V & Benhamou, Y 2016, ‘Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura’, Journal of Thrombosis & Haemostasis, vol. 14, no. 10, p. 1917, viewed 24 August 2019, .
    • MLA:
      Le Besnerais, M., et al. “Assessment of Endothelial Damage and Cardiac Injury in a Mouse Model Mimicking Thrombotic Thrombocytopenic Purpura.” Journal of Thrombosis & Haemostasis, vol. 14, no. 10, Oct. 2016, p. 1917. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082.
    • Chicago/Turabian: Humanities:
      Le Besnerais, M., J. Favre, C. V. Denis, P. Mulder, J. Martinet, L. Nicol, H. Levesque, et al. “Assessment of Endothelial Damage and Cardiac Injury in a Mouse Model Mimicking Thrombotic Thrombocytopenic Purpura.” Journal of Thrombosis & Haemostasis 14, no. 10 (October 2016): 1917. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082.
    • Vancouver/ICMJE:
      Le Besnerais M, Favre J, Denis CV, Mulder P, Martinet J, Nicol L, et al. Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura. Journal of Thrombosis & Haemostasis [Internet]. 2016 Oct [cited 2019 Aug 24];14(10):1917. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=119103082