Published online before print May 9, 2002, doi: 10.1161/01.RES.0000021044.53156.F5
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Submitted on October 12, 2001
Revised on April 11, 2002
Accepted on April 22, 2002
Adenoviral Activin A Expression Prevents Intimal Hyperplasia in Human and Murine Blood Vessels by Maintaining the Contractile Smooth Muscle Cell Phenotype
Marten A. Engelse ;
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.
* To whom correspondence should be addressed. 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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