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01-09-2010 | Original Contribution

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum

Authors: Enrico Lupia, Tiziana Spatola, Alessandra Cuccurullo, Ornella Bosco, Filippo Mariano, Angela Pucci, Roberta Ramella, Giuseppe Alloatti, Giuseppe Montrucchio

Published in: Basic Research in Cardiology | Issue 5/2010

Abstract

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-α and IL-1β. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-α and IL-1β in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

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Title: Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum
Authors: Enrico Lupia
Tiziana Spatola
Alessandra Cuccurullo
Ornella Bosco
Filippo Mariano
Angela Pucci
Roberta Ramella
Giuseppe Alloatti
Giuseppe Montrucchio
Publication date: 01-09-2010
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 5/2010
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-010-0103-6

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Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum

Abstract

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