Abstract
Vascular proliferative disorders are characterized by the proliferation of vascular smooth muscle cells (SMCs) and excessive extracellular matrix synthesis. We found that bone morphogenetic protein-2 (BMP-2) inhibited serum-stimulated increases in DNA synthesis and cell number of cultured rat arterial SMCs in a fashion quite different from that in the case of transforming growth factor-beta1 (TGF-beta1). In addition, TGF-beta1 stimulated collagen synthesis in SMCs, whereas BMP-2 did not. In an in vivo rat carotid artery balloon injury model, the adenovirus-mediated transfer of the BMP-2 gene inhibited injury-induced intimal hyperplasia. These results indicate that BMP-2 has the ability to inhibit SMC proliferation without stimulating extracellular matrix synthesis, and suggest the possibility of therapeutic application of BMP-2 for the prevention of vascular proliferative disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Aorta
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / pharmacology*
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Carotid Arteries / cytology
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Carotid Artery Injuries
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Catheterization
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Cell Division / drug effects
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Cells, Cultured
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Collagen / biosynthesis
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DNA / biosynthesis
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Gene Transfer Techniques
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Growth Inhibitors / genetics
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Growth Inhibitors / pharmacology*
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Humans
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects*
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Rats
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Rats, Wistar
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology
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Recombinant Proteins
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Transforming Growth Factor beta / pharmacology
Substances
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BMP2 protein, human
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Bmp2 protein, rat
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Growth Inhibitors
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Recombinant Fusion Proteins
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Recombinant Proteins
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Transforming Growth Factor beta
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recombinant human bone morphogenetic protein-2
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Collagen
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DNA