C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization

Kentaro Doi, Tadashi Ikeda, Hiroshi Itoh, Koji Ueyama, Kiminori Hosoda, Yoshihiro Ogawa, Jun Yamashita, Tae Hwa Chun, Mayumi Inoue, Ken Masatsugu, Naoki Sawada, Yasutomo Fukunaga, Takatoshi Saito, Masakatsu Sone, Kenichi Yamahara, Hyun Kook, Masashi Komeda, Makiko Ueda, Kazuwa Nakao

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64 Citations (Scopus)

Abstract

We recently reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts as a vascular-type natriuretic peptide. In the present study, we stimulated the cGMP cascade in proliferating smooth muscle cells (SMCs), in which particulate guanylate cyclase-B, the specific receptor for CNP, is predominantly expressed, by use of an adenovirus encoding rat CNP cDNA (Ad.CNP). In the Ad.CNP-treated cultured SMCs, CNP caused the growth inhibition of SMCs at G1, phase with an early increase of p21CIP1/WAF1 expression and subsequent upregulation of p16INK4a. The expression of smooth muscle myosin heavy chain-2, which is the molecular marker of highly differentiated SMCs, was reinduced in the Ad.CNP-treated SMCs. The Ad.CNP-treated SMCs also reexpressed particulate guanylate cyclase-A, which shows high affinity to atrial and brain natriuretic peptide and is exclusively expressed in well-differentiated SMCs. CNP, which was overexpressed in rabbit femoral arteries in vivo at the time of balloon injury, significantly suppressed neointimal formation. Furthermore, an enhancement of the expression of smooth muscle myosin heavy chain-2 occurred in the residual neointima. In addition, early regeneration of endothelial cells was observed in the Ad.CNP-infected group. Thus, stimulation of cGMP cascade in proliferating dedifferentiated SMCs can induce growth inhibition and redifferentiation of SMCs with accelerated reendothelialization.

Original languageEnglish
Pages (from-to)930-936
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume21
Issue number6
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Keywords

  • Adenovirus
  • C-type natriuretic peptide
  • Endothelial cells
  • Gene therapy
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Doi, K., Ikeda, T., Itoh, H., Ueyama, K., Hosoda, K., Ogawa, Y., Yamashita, J., Chun, T. H., Inoue, M., Masatsugu, K., Sawada, N., Fukunaga, Y., Saito, T., Sone, M., Yamahara, K., Kook, H., Komeda, M., Ueda, M., & Nakao, K. (2001). C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(6), 930-936. https://doi.org/10.1161/01.ATV.21.6.930