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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:405.)
© 2002 American Heart Association, Inc.

Vascular Biology

Different Effects of High and Low Shear Stress on Platelet-Derived Growth Factor Isoform Release by Endothelial Cells

Consequences for Smooth Muscle Cell Migration

Roberta Palumbo^*; Carlo Gaetano^*; Annalisa Antonini; Giulio Pompilio; Enrico Bracco; Lars Rönnstrand; Carl-Henrik Heldin; Maurizio C. Capogrossi

From the Centro Cardiologico Monzino (R.P., G.P.), Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy; Laboratorio di Patologia Vascolare (C.G., A.A., M.C.C.), Istituto Dermopatico dell’Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy; and the Ludwig Institute for Cancer Research (E.B., L.R., C.-H.H.), Biomedical Center, Uppsala, Sweden.

Correspondence to Dr Carlo Gaetano, Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata, Via dei Monti di Creta 104, 0167 Rome, Italy. E-mail gaetano{at}idi.it

In the present study, we analyzed the effect of conditioned media (CM) from bovine aortic endothelial cells exposed to laminar shear stress (SS) of 5 dyne/cm² (SS5) or 15 dyne/cm² (SS15) for 16 hours on smooth muscle cell (SMC) migration. In response to CM from bovine aortic endothelial cells exposed to SS5 (CMSS5) and SS15 (CMSS15), migration was 45±5.5 and 30±1.5 cells per field, respectively (P<0.05). Similar results were obtained with SS of 2 versus 20 dyne/cm² and also when SS of 5 and 15 dyne/cm² lasted 24 hours. Platelet-derived growth factor (PDGF)-AA levels in CMSS5 and CMSS15 were 9±7 and 18±5 ng/10⁶ cells for 16 hours, respectively (P<0.05); PDGF-BB levels in CMSS5 and CMSS15 were 38±10 and 53±10 ng/10⁶ cells for 16 hours, respectively (P<0.05). PDGF receptor (PDGFR) and PDGF receptor ß (PDGFRß) in SMCs were phosphorylated by CMSS15>CMSS5. In response to CMSS15, a neutralizing antibody against PDGF-AA enhanced SMC migration to a level comparable to that of CMSS5; in contrast, antibodies against PDGF-BB abolished SMC migration. Transfection of SMCs with a dominant-negative PDGFR or PDGFRß increased or inhibited, respectively, SMC migration in response to CMSS15. Overexpression of wild-type PDGFR inhibited SMC migration in response to CMSS5, CMSS15, or recombinant PDGF-BB (P<0.001). These results suggest that the ability of high SS to inhibit arterial wall thickening in vivo may be related to enhanced activation of PDGFR in SMCs by PDGF isoforms secreted by the endothelium.

Key Words: shear stress • endothelial cells • smooth muscle cells • platelet-derived growth factors • platelet-derived growth factor receptors

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