Inhibition of rat vascular smooth muscle proliferation in vitro and in vivo by bone morphogenetic protein-2

• Published in: The Journal of clinical investigation Vol. 100; no. 11; pp. 2824 - 2832
• Main Authors: Nakaoka, T, Gonda, K, Ogita, T, Otawara-Hamamoto, Y, Okabe, F, Kira, Y, Harii, K, Miyazono, K, Takuwa, Y, Fujita, T
• Format: Journal Article
• Language: English
• Published: United States 01.12.1997
• Subjects: Adenoviridae - genetics; Animals; Aorta; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - pharmacology; Carotid Arteries - cytology; Carotid Artery Injuries; Catheterization; Cell Division - drug effects; Cells, Cultured; Collagen - biosynthesis; DNA - biosynthesis; Gene Transfer Techniques; Growth Inhibitors - genetics; Growth Inhibitors - pharmacology; Humans; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Rats; Rats, Wistar; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacology; Recombinant Proteins; Transforming Growth Factor beta - pharmacology
• ISSN: 0021-9738
• DOI: 10.1172/jci119830

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.