title: A novel role of thrombopoietin as a physiological modulator of coronary flow.
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 (P(Ser1179)) 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; 10nM) 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.
authors.affiliation: Department of Animal and Human Biology, University of Turin, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ramella
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Gallo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Spatola
authors.forename: Enrico
authors.initials: E
authors.lastname: Lupia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Alloatti
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism*; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D019332:Endothelin-1; D053628:Receptors, Thrombopoietin; D009569:Nitric Oxide; D013926:Thrombopoietin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D019331:NG-Nitroarginine Methyl Ester; D000077191:Wortmannin