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

Biochem Biophys Res Commun. 1997 Oct 29;239(3):889-94. doi: 10.1006/bbrc.1997.7576.


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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Aorta, Thoracic
  • Atrial Natriuretic Factor / biosynthesis
  • Atrial Natriuretic Factor / genetics*
  • Cells, Cultured
  • Cyclic GMP / metabolism
  • Cyclin A / biosynthesis
  • Cyclin A / genetics
  • G1 Phase / genetics*
  • Gene Expression Regulation
  • Gene Transfer Techniques*
  • Growth Inhibitors / genetics*
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / virology
  • Natriuretic Peptide, C-Type
  • Protein Biosynthesis
  • Proteins / genetics*
  • RNA, Messenger / biosynthesis
  • Rats


  • Cyclin A
  • Growth Inhibitors
  • Proteins
  • RNA, Messenger
  • Natriuretic Peptide, C-Type
  • Atrial Natriuretic Factor
  • Cyclic GMP