Thrombopoietin (TPO) is known for its ability to stimulate platelet production. However, little is currently known whether TPO plays a physiological function in the heart. The potential vasodilatory role of TPO was tested on the isolated rat heart. The expression of TPO receptor (c-mpl) and the TPO-dependent eNOS phosphorylation (PSer1179) were studied on Cardiac-derived normal Human Micro Vascular Endothelial Cells (HMVEC-C) by Western blot analysis. While TPO (10–200 pg/mL) did not modify coronary flow (CF) under basal conditions, it reduced the coronary constriction caused by endothelin-1 (ET-1; 10 nM) in a dose-dependent manner. This effect was blocked by both Wortmannin (100 nM) and L-NAME (100 nM); on HMVEC-C, TPO induced eNOS phosphorylation through a Wortmannin sensitive mechanism. Taken together, our data suggest a potential role of TPO as a physiological regulator of CF. By acting on specific receptors present on endothelial cells, TPO may induce PI3K/Akt-dependent eNOS phosphorylation and NO release.

A novel role of thrombopoietin as a physiological modulator of coronary flow

RAMELLA, Roberta;GALLO, Maria Pia;SPATOLA, Tiziana;LUPIA, Enrico;ALLOATTI, Giuseppe
2011-01-01

Abstract

Thrombopoietin (TPO) is known for its ability to stimulate platelet production. However, little is currently known whether TPO plays a physiological function in the heart. The potential vasodilatory role of TPO was tested on the isolated rat heart. The expression of TPO receptor (c-mpl) and the TPO-dependent eNOS phosphorylation (PSer1179) were studied on Cardiac-derived normal Human Micro Vascular Endothelial Cells (HMVEC-C) by Western blot analysis. While TPO (10–200 pg/mL) did not modify coronary flow (CF) under basal conditions, it reduced the coronary constriction caused by endothelin-1 (ET-1; 10 nM) in a dose-dependent manner. This effect was blocked by both Wortmannin (100 nM) and L-NAME (100 nM); on HMVEC-C, TPO induced eNOS phosphorylation through a Wortmannin sensitive mechanism. Taken together, our data suggest a potential role of TPO as a physiological regulator of CF. By acting on specific receptors present on endothelial cells, TPO may induce PI3K/Akt-dependent eNOS phosphorylation and NO release.
2011
167
5
8
Thrombopoietin; Coronary flow; Endothelium; Nitric Oxide
Roberta Ramella; Maria Pia Gallo; Tiziana Spatola; Enrico Lupia; Giuseppe Alloatti
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/79666
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