1997年10月
Adenovirus-mediated gene transfer of C-type natriuretic peptide causes G1 growth inhibition of cultured vascular smooth muscle cells
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- 巻
- 239
- 号
- 3
- 開始ページ
- 889
- 終了ページ
- 894
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1006/bbrc.1997.7576
- 出版者・発行元
- ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
We have proposed the ''vascular natriuretic peptide system'', in which C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, can control vascular tone and growth as an endothelium-derived relaxing peptide. We aimed at overexpression of CNP gene in vascular smooth muscle cells (SMCs) by adenovirus-mediated gene transfer to examine the growth characteristics of SMCs via the augmentation of cGMP production, Rat aortic SMCs infected with Ad.CNP, a replication-deficient adenovirus driving rat CNP cDNA, produced 162+/-55 fmol/mL of CNP, which was 4,000 times higher than that produced by endothelial cells. cGMP production was also augmented in Ad.CNP-infected SMCs (2200+/-270 fmol/10(4) cells). Accordingly, significant growth inhibition was observed in SMCs infected with Ad.CNP. The flow cytometry analysis revealed that the population of the S and G2+M phases was reduced by 60% of the control in Ad.CNP-infected SMCs. The gene expression of ANP-B receptor, which is expressed abundantly in SMCs with the synthetic phenotype, was suppressed in Ad.CNP-infected SMCs, while the gene expression of ANP-A receptor, which is expressed predominantly in SMCs with the contractile phenotype, became detectable in Ad.CNP-infected SMCs. In addition, the gene expression of smooth muscle myosin heavy chain-a (SM-2), which is the molecular marker of highly-differentiated SMCs, was also induced in Ad.CNP-treated SMCs. These results suggest that cGMP cascade activation induces re-differentiation of SMCs. The present study demonstrated that overexpression of CNP induced growth inhibition of SMCs at the G1 phase with possible alteration of the phenotype. (C) 1997 Academic Press.
- リンク情報
- ID情報
-
- DOI : 10.1006/bbrc.1997.7576
- ISSN : 0006-291X
- PubMed ID : 9367865
- Web of Science ID : WOS:A1997YG93100046