Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide

N. Ohno, Hiroshi Itoh, T. Ikeda, K. Ueyama, K. Yamahara, K. Doi, J. Yamashita, M. Inoue, K. Masatsugu, N. Sawada, Y. Fukunaga, S. Sakaguchi, M. Sone, T. Yurugi, H. Kook, M. Komeda, K. Nakao

Research output: Contribution to journalArticle

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Abstract

Background - Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. Methods and Results - Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81±0.05 versus 0.30±0.14, P<0.01) and at 28 days (0.96±0.01 versus 0.45±0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. Conclusions - Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Original languageEnglish
Pages (from-to)1623-1626
Number of pages4
JournalCirculation
Volume105
Issue number14
DOIs
Publication statusPublished - 2002 Apr 9
Externally publishedYes

Fingerprint

C-Type Natriuretic Peptide
Jugular Veins
Adenoviridae
Hyperplasia
Rabbits
Transplants
Genes
Veins
Thrombosis
Coronary Vessels
Lac Operon
Wounds and Injuries
Atrial Natriuretic Factor
Vascular Smooth Muscle
Carotid Arteries
Smooth Muscle Myocytes
Endothelial Cells

Keywords

  • Genes
  • Grafting
  • Natriuretic peptides
  • Viruses

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide. / Ohno, N.; Itoh, Hiroshi; Ikeda, T.; Ueyama, K.; Yamahara, K.; Doi, K.; Yamashita, J.; Inoue, M.; Masatsugu, K.; Sawada, N.; Fukunaga, Y.; Sakaguchi, S.; Sone, M.; Yurugi, T.; Kook, H.; Komeda, M.; Nakao, K.

In: Circulation, Vol. 105, No. 14, 09.04.2002, p. 1623-1626.

Research output: Contribution to journalArticle

Ohno, N, Itoh, H, Ikeda, T, Ueyama, K, Yamahara, K, Doi, K, Yamashita, J, Inoue, M, Masatsugu, K, Sawada, N, Fukunaga, Y, Sakaguchi, S, Sone, M, Yurugi, T, Kook, H, Komeda, M & Nakao, K 2002, 'Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide', Circulation, vol. 105, no. 14, pp. 1623-1626. https://doi.org/10.1161/01.CIR.0000014985.50017.6E
Ohno, N. ; Itoh, Hiroshi ; Ikeda, T. ; Ueyama, K. ; Yamahara, K. ; Doi, K. ; Yamashita, J. ; Inoue, M. ; Masatsugu, K. ; Sawada, N. ; Fukunaga, Y. ; Sakaguchi, S. ; Sone, M. ; Yurugi, T. ; Kook, H. ; Komeda, M. ; Nakao, K. / Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide. In: Circulation. 2002 ; Vol. 105, No. 14. pp. 1623-1626.
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abstract = "Background - Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. Methods and Results - Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81±0.05 versus 0.30±0.14, P<0.01) and at 28 days (0.96±0.01 versus 0.45±0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. Conclusions - Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.",
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AU - Ohno, N.

AU - Itoh, Hiroshi

AU - Ikeda, T.

AU - Ueyama, K.

AU - Yamahara, K.

AU - Doi, K.

AU - Yamashita, J.

AU - Inoue, M.

AU - Masatsugu, K.

AU - Sawada, N.

AU - Fukunaga, Y.

AU - Sakaguchi, S.

AU - Sone, M.

AU - Yurugi, T.

AU - Kook, H.

AU - Komeda, M.

AU - Nakao, K.

PY - 2002/4/9

Y1 - 2002/4/9

N2 - Background - Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. Methods and Results - Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81±0.05 versus 0.30±0.14, P<0.01) and at 28 days (0.96±0.01 versus 0.45±0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. Conclusions - Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

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