451. Different effects of high and low shear stress on platelet-derived growth factor isoform release by endothelial cells: consequences for smooth muscle cell migration.
- Author
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Palumbo R, Gaetano C, Antonini A, Pompilio G, Bracco E, Rönnstrand L, Heldin CH, and Capogrossi MC
- Subjects
- Animals, Becaplermin, Cattle, Culture Media, Conditioned pharmacology, Endothelium, Vascular physiology, Muscle, Smooth, Vascular drug effects, Mutation, Phosphorylation, Platelet-Derived Growth Factor pharmacology, Proto-Oncogene Proteins c-sis, Receptor, Platelet-Derived Growth Factor alpha genetics, Receptor, Platelet-Derived Growth Factor alpha physiology, Receptor, Platelet-Derived Growth Factor beta genetics, Receptor, Platelet-Derived Growth Factor beta physiology, Stress, Mechanical, Transfection, Chemotaxis, Endothelium, Vascular metabolism, Muscle, Smooth, Vascular physiology, Platelet-Derived Growth Factor biosynthesis
- Abstract
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/10(6) cells for 16 hours, respectively (P<0.05); PDGF-BB levels in CMSS5 and CMSS15 were 38 +/- 10 and 53 +/- 10 ng/10(6) cells for 16 hours, respectively (P<0.05). PDGF receptor alpha (PDGFRalpha) and PDGF receptor beta (PDGFRbeta) 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 PDGFRalpha or PDGFRbeta increased or inhibited, respectively, SMC migration in response to CMSS15. Overexpression of wild-type PDGFRalpha 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 PDGFRalpha in SMCs by PDGF isoforms secreted by the endothelium.
- Published
- 2002
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