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PMID: 9389748 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 100 ·No. 11 ·1997-12-01 ·Pages 2824-32

Nakaoka T, Gonda K, Ogita T, Otawara-Hamamoto Y, Okabe F, Kira Y, Harii K, Miyazono K, Takuwa Y, Fujita T

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.

MeSH Terms
Adenoviridae/genetics Animals Aorta Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins/genetics,pharmacology Carotid Arteries/cytology Carotid Artery Injuries Catheterization Cell Division/drug effects Cells, Cultured Collagen/biosynthesis DNA/biosynthesis Gene Transfer Techniques Growth Inhibitors/genetics,pharmacology Humans Muscle, Smooth, Vascular/cytology,drug effects Rats Rats, Wistar Recombinant Fusion Proteins/genetics,pharmacology Recombinant Proteins Transforming Growth Factor beta/pharmacology
Chemicals
BMP2 protein, human Bmp2 protein, rat Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins Growth Inhibitors Recombinant Fusion Proteins Recombinant Proteins Transforming Growth Factor beta recombinant human bone morphogenetic protein-2 Collagen DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Nakaoka T
Fourth Department of Internal Medicine, School of Medicine, University of Tokyo, Tokyo 112, Japan.
Gonda K
Ogita T
Otawara-Hamamoto Y
Okabe F
Kira Y
Harii K
Miyazono K
Takuwa Y
Fujita T
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119830
Published
1997-12-01
Pages
2824-32
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508488
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI119830 PMC Full Text View journal details
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