Adenovirus-mediated gene transfer of C-type natriuretic peptide causes G1 growth inhibition of cultured vascular smooth muscle cells

Kentaro Doi, Hiroshi Itoh, Tadashi Ikeda, Kiminori Hosoda, Yoshihiro Ogawa, Toshio Igaki, Jun Yamashita, Tae Hwa Chun, Mayumi Inoue, Ken Masatsugu, Katsuhiko Matsuda, Katsuyuki Ohmori, Kazuwa Nakao

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22 Citations (Scopus)

Abstract

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 4000 times higher than that produced by endothelial cells. cGMP production was also augmented in Ad.CNP-infected SMCs (2200 ± 270 fmol/104 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-2 (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.

Original languageEnglish
Pages (from-to)889-894
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume239
Issue number3
DOIs
Publication statusPublished - 1997 Oct 29
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Doi, K., Itoh, H., Ikeda, T., Hosoda, K., Ogawa, Y., Igaki, T., Yamashita, J., Chun, T. H., Inoue, M., Masatsugu, K., Matsuda, K., Ohmori, K., & Nakao, K. (1997). Adenovirus-mediated gene transfer of C-type natriuretic peptide causes G1 growth inhibition of cultured vascular smooth muscle cells. Biochemical and Biophysical Research Communications, 239(3), 889-894. https://doi.org/10.1006/bbrc.1997.7576