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(Circulation Research. 2002;90:1128.)
© 2002 American Heart Association, Inc.

Integrative Physiology

Adenoviral Activin A Expression Prevents Intimal Hyperplasia in Human and Murine Blood Vessels by Maintaining the Contractile Smooth Muscle Cell Phenotype

Marten A. Engelse^*, JanWillem H.P. Lardenoye^*, Jolanda M. Neele, Jos M. Grimbergen, Margreet R. de Vries, Martine L.M. Lamfers, Hans Pannekoek, Paul H.A. Quax, Carlie J.M. de Vries

From the Academic Medical Center (M.A.E., J.M.N., H.P., C.J.M.d.V.), University of Amsterdam, Department of Biochemistry, Amsterdam, The Netherlands; and Gaubius Laboratory (J.H.P.L., J.M.G., M.R.d.V., M.L.M.L., P.H.A.Q.), TNO-PG, Leiden, The Netherlands. Present address for M.A.E. is Gaubius Laboratory, TNO-PG, Leiden, The Netherlands.

Correspondence to Carlie J.M. de Vries, PhD, Dept of Biochemistry, Academic Medical Center, K1-163, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail c.j.devries{at}amc.uva.nl

Activin A alters the characteristics of human arterial smooth muscle cells (SMCs) toward a contractile, quiescent phenotype. We hypothesize that activin A may prevent SMC-rich neointimal hyperplasia. Here, we study the effect of adenovirus-mediated expression of activin A on neointima formation in vitro and in vivo. Human saphenous vein organ cultures, in which a neointima is formed spontaneously, were infected either with activin A- or lacZ-adenovirus. Activin A-overexpression reduces neointima formation by 78%, whereas no significant reduction was observed after control infection. In addition, the effect of activin A on neointima formation was assessed in vivo in mice with cuffed femoral arteries. In activin A adenovirus-infected mice (IV injection), neointimal hyperplasia is reduced by 77% compared with the SMC-rich neointima in mock-infected or in noninfected mice. Cultured human saphenous vein SMCs and murine aorta SMCs were incubated with activin A and an increased expression of SM22 and SM -actin mRNA, and SM -actin protein was demonstrated. Laser-capture microdissection on sections of cuffed murine arteries and subsequent real-time RT-PCR established in vivo induction of SM -actin mRNA in the media of activin A–treated mice. In summary, activin A inhibits neointima formation in vitro and in vivo by preventing SMC dedifferentiation.

Key Words: cuff model • adenovirus • transforming growth factor-ß • smooth muscle cell • laser-capture microdissection

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