Endothelial cell conditioned media downregulates smooth muscle
contractile protein expression.
Vernon, Sarah M., Manuel J. Campos, Timothy Haystead, Maria M.
Thompson, Paul E. Dicorleto, and Gary K. Owens.
Departments of Medicine (Cardiology), Molecular Physiology and
Biological Physics, and Pharmacology, University of Virginia School
of Medicine, Charlottesville, Virginia 22908; Department of Cell
Biology, Research Institute, Cleveland Clinic Foundation, Cleveland,
Ohio, 44195
APStracts 3:0299C, 1996.
Smooth muscle cells (SMC) within atherosclerotic lesions proliferate
and exhibit phenotypic modulation, but the contribution of vascular
endothelium to this process is poorly understood. Our aim was to
examine the effects of endothelial cell conditioned media (ECCM) on
vascular SMC growth and differentiation. Rat aortic ECCM stimulated a
9-fold increase in 3H-thymidine incorporation and downregulated SM
-specific myosin heavy chain (MHC) and a-actin synthesis in rat aortic
SMC. These effects were not inhibited by antibodies to platelet
-derived growth factor (PDGF)-BB or PDGF-AB, or with a PDGF [beta]
-receptor subunit. Treatment with PDGF-BB (at concentration found in
ECCM), PDGF-AA, bFGF, endothelin-1, or transforming growth factor
-[beta] did not reproduce these effects. The ECCM activities were
sensitive to heat and trypsinization, >30 kDa molecular size
and bound weakly to heparin-sepharose. Our data indicate that
cultured EC produce a factor(s) that downregulates contractile
protein expression in SMC which may contribute to SMC de
-differentiation and proliferation.
Received 26 December 1995; accepted in final form 16 September
1996.
APS Manuscript Number C763-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996