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Am J Physiol Heart Circ Physiol 265: H3-H8, 1993;
0363-6135/93 $5.00
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AJP - Heart and Circulatory Physiology, Vol 265, Issue 1 3-H8, Copyright © 1993 by American Physiological Society

ARTICLES

Fluid shear stress stimulates platelet-derived growth factor expression in endothelial cells

M. Mitsumata, R. S. Fishel, R. M. Nerem, R. W. Alexander and B. C. Berk
School of Mechanical Engineering, Georgia Institute of Technology, Atlanta 30332-0405.

Fluid flow and the associated shear stress play a critical role in vascular growth and remodeling. Recent data suggest that increased endothelial cell expression of platelet-derived growth factor (PDGF) A- and B-chain by flow may participate in these events. In the present study, we examined the mechanism for flow-induced PDGF expression, focusing on protein kinase C (PKC). Bovine aortic endothelial cells were exposed to flow (shear stress = 30 dyn/cm2) in a parallel-plate flow chamber. Increases in PDGF B-chain, but not PDGF A-chain, were observed within 3 h, maximal within 6 h (13-fold increase), and sustained for 24 h. PKC appeared to be involved because phorbol 12-myristate 13-acetate induced PDGF B-chain mRNA. Activation of PKC alone, however, was insufficient to induce PDGF mRNA because the selective PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, did not induce PDGF expression. A PKC-independent pathway was suggested by the fact that inhibition of PKC (downregulation with phorbol 12,13-dibutyrate or exposure to staurosporine) failed to block PMA or flow-induced PDGF B-chain expression. These results demonstrate flow-induced PDGF B-chain expression in endothelial cells that appears to be mediated, in part, by a PKC-independent pathway.


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