Titre du document / Document title

Biphasic effect of pioglitazone on isolated human endothelial progenitor cells: Involvement of peroxisome proliferator-activated receptor-γ and transforming growth factor-β 1

Auteur(s) / Author(s)

REDONDO Santiago ^{(1 2)} ; HRISTOV Mihail ^{(2 3)} ; GÜMBEL Denis ⁽²⁾ ; TEJERINA Teresa ⁽¹⁾ ; WEBER Christian ^{(2 3)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, ESPAGNE
⁽²⁾ Institute for Molecular Cardiovascular Research (IMCAR), Aachen, ALLEMAGNE
⁽³⁾ Interdisciplinary Center for Clinical Research "BIOMAT", RWTH University Hospital, Aachen, ALLEMAGNE

Résumé / Abstract

Endothelial progenitor cells (EPCs) have been implicated in vascular repair and found to be functionally impaired in patients with diabetes.We evaluated the effects of the anti-diabetic drug pioglitazone on human EPC function and the involvement of PPAR-γ and TGF-β1. EPCs in culture were characterized at day 7 by the development of colony-forming units (CFUs) and flow cytometry assessment of differentiation marker (Dil-ac-LDL/ lectin, KDR and CD31).Adhesion on fibronectin and fibrinogen in flow was analyzed as functional parameter. Treatment with pioglitazone for 72 hours increased the number of EPC-CFUs, Dil-ac-LDL⁺/lectin⁺, CD31⁺ and KDR⁺ EPCs at I μM but not at 10 μM. Since pioglitazone did not significantly alter proliferation and apoptosis in cultured EPCs,the increase in EPC number was most likely attributable to augmented adhesion and differentiation. Indeed, pioglitazone increased EPC adhesion in flow at I μM, an effect prevented by PPAR-γ and β2-integrin blockade. In contrast, pioglitazone did not promote EPC adhesion at 10 μM; however, increased adhesion became evident by co-incubation with a blocking TGF-β1 antibody. As determined by ELISA, pioglitazone induced a persistent increase in TGF-β I secretion only at 10 μM when a significantly elevated expression of endoglin,the accessory receptor forTGF-β I,was also observed. Taken together, pioglitazone exerts biphasic effects on the function of isolated EPCs, causing a PPAR-γ-dependent stimulation at I μM and a TGF-β1-mediated suppression at 10 μM.These results may help to define optimal therapeutic doses of pioglitazone for improving endothelial dysfunction.

Revue / Journal Title

Thrombosis and haemostasis   ISSN 0340-6245   CODEN THHADQ 

Source / Source

2007, vol. 97, n^o6, pp. 979-987 [9 page(s) (article)] (45 ref.)

Langue / Language

Anglais

Editeur / Publisher

Schattauer, Stuttgart, ALLEMAGNE  (1976) (Revue)

Mots-clés anglais / English Keywords

Thiazolidinedione derivatives ; Peroxisome proliferator activated receptor gamma ; Adhesion ; Growth factor ; Pharmacology ; Transforming growth factor β ; Stem cell ; Endothelial cell ; Human ; Isolated cell ; Pioglitazone ;

Mots-clés français / French Keywords

Thiazolidinedione dérivé ; Récepteur PPAR-γ ; Adhérence ; Facteur croissance ; Pharmacologie ; Facteur croissance transformant β ; Cellule souche ; Cellule endothéliale ; Homme ; Cellule isolée ; Pioglitazone ;

Mots-clés espagnols / Spanish Keywords

Tiazolidinediona derivado ; Adherencia ; Factor crecimiento ; Farmacología ; Factor crecimiento transformante β ; Célula primitiva ; Célula endotelial ; Hombre ; Célula aislada ; Pioglitazona ;

Mots-clés d'auteur / Author Keywords

Endothelial ; pioglitazone ; pharmacology ; growth factors ; adhesion ;

Localisation / Location

INIST-CNRS, Cote INIST : 10255, 35400016231707.0160