© 1999 American Heart Association, Inc.
Cellular Biology |
Human Activin-A Is Expressed in the Atherosclerotic Lesion and Promotes the Contractile Phenotype of Smooth Muscle Cells
From the Academic Medical Center (M.A.E., J.M.N., T.A.E.v.A., B.E.v.A., H.P., C.J.M.d.V.), University of Amsterdam, Department of Biochemistry, Amsterdam and Erasmus University (R.H.N.v.S.), Department of Endocrinology and Reproduction, Rotterdam, The Netherlands.
Correspondence to Carlie J.M. de Vries, PhD, Department of Biochemistry, Academic Medical Center K1-163, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail c.j.devries{at}amc.uva.nl
Abstract—Activin is a member of
the transforming growth factor-ß superfamily, and it modulates the
proliferation and differentiation of various target cells. In this
study, we investigated the role of activin in the initiation and
progression of human atherosclerosis. The expression of
activin, its physiological inhibitor
follistatin, and activin receptors were assayed in human vascular
tissue specimens that represented various stages of
atherogenesis. In situ hybridization experiments revealed activin mRNA
in endothelial cells and macrophages and a
strong induction of activin expression in neointimal smooth
muscle cells from the early onset of atherogenesis. We developed an
"in situ free-activin binding assay" by using biotinylated
follistatin, which allowed us to detect bioactive activin at specific
sites in atherosclerotic lesions. The mRNAs encoding the activin
receptors are expressed similarly in normal and atherosclerotic tissue,
which indicates that activin-A signaling in atherogenesis is most
likely dependent on changes in growth factor concentrations rather than
on receptor levels. In vitro, activin induces the contractile,
nonproliferative phenotype in cultured smooth muscle cells, as
is reflected by increased expression of smooth muscle-specific markers
(SM
-actin and SM22). Our data provide evidence that
activin induces redifferentiation of neointimal smooth
muscle cells, and we hypothesize that activin is involved in
plaque stabilization.
Key Words: atherosclerosis • smooth muscle cell • follistatin • transforming growth factor-ß
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