Adenoviral activin a expression prevents intimal hyperplasia in human and murine blood vessels by maintaining the contractile smooth muscle cell phenotype.

Abstract

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 SM22alpha and SM alpha-actin mRNA, and SM alpha-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 alpha-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.

• Authors: 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
• Journal: Circulation research (Circ Res) Vol. 90 Issue 10 Pg. 1128-34 (May 31 2002) ISSN: 1524-4571 [Electronic] United States
• PMID: 12039804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Muscle Proteins
• RNA, Messenger
• activin A
• Activins
• Inhibin-beta Subunits

Topics

• Activins (genetics, metabolism, pharmacology)
• Adenoviridae (genetics)
• Animals
• Arterial Occlusive Diseases (metabolism, pathology, prevention & control)
• Cell Differentiation
• Cell Line
• Cells, Cultured
• Femoral Artery (cytology, pathology)
• Genetic Vectors
• Humans
• Hyperplasia
• Inhibin-beta Subunits (genetics, metabolism, pharmacology)
• Kinetics
• Mice
• Muscle Contraction
• Muscle Proteins (biosynthesis, genetics)
• Muscle, Smooth, Vascular (drug effects, metabolism, physiology)
• Organ Culture Techniques
• Phenotype
• RNA, Messenger (biosynthesis)
• Saphenous Vein (anatomy & histology, cytology)
• Tunica Intima (pathology)