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 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.
Nakaoka
T
T
Fourth Department of Internal Medicine, School of Medicine, University of Tokyo, Tokyo 112, Japan.
Gonda
K
K
Ogita
T
T
Otawara-Hamamoto
Y
Y
Okabe
F
F
Kira
Y
Y
Harii
K
K
Miyazono
K
K
Takuwa
Y
Y
Fujita
T
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D002339:Carotid Arteries / Q000166:cytology; D020212:Carotid Artery Injuries; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D018014:Gene Transfer Techniques; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D006131:Growth Inhibitors; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen; D004247:DNA