TY - JOUR
T1 - Adenovirus-mediated gene transfer of C-type natriuretic peptide causes G1 growth inhibition of cultured vascular smooth muscle cells
AU - Doi, Kentaro
AU - Itoh, Hiroshi
AU - Ikeda, Tadashi
AU - Hosoda, Kiminori
AU - Ogawa, Yoshihiro
AU - Igaki, Toshio
AU - Yamashita, Jun
AU - Chun, Tae Hwa
AU - Inoue, Mayumi
AU - Masatsugu, Ken
AU - Matsuda, Katsuhiko
AU - Ohmori, Katsuyuki
AU - Nakao, Kazuwa
PY - 1997/10/29
Y1 - 1997/10/29
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1997.7576
DO - 10.1006/bbrc.1997.7576
M3 - Article
C2 - 9367865
AN - SCOPUS:0031590430
VL - 239
SP - 889
EP - 894
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -