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

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 Pat arterial SMCs in a fashion quite different from that in the case of transforming growth factor-beta 1 (TGF-beta 1). In addition, TGF-beta 1 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.