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Am J Physiol Heart Circ Physiol 288: H2203-H2209, 2005. First published January 6, 2005; doi:10.1152/ajpheart.00555.2004
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Antisense oligodeoxyribonucleotide as to the growth factor midkine suppresses neointima formation induced by balloon injury

Kenji Hayashi ,1,* Hiroshi Banno,1,2,* Kenji Kadomatsu,1 Yoshifumi Takei,1 Kimihiro Komori,2 and Takashi Muramatsu1

Departments of 1Biochemistry and 2Vascular Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

Submitted 8 June 2004 ; accepted in final form 30 December 2004

Restenosis is the major clinical problem of angioplasty. We have previously shown that neointima formation is strikingly suppressed in midkine (MK)-deficient mice. Neointima formation is restored if MK protein is administrated to the deficient mice. MK is a heparin-binding growth factor and implicated in the migration of inflammatory cells and vascular smooth muscle cells. Consistently, the suppression of neointima formation in the deficient mice is accompanied by suppression of recruitment of inflammatory cells into the vascular wall. Here, we evaluated the potential of MK antisense oligodeoxyribonucleotide (ODN) for the prevention of restenosis. We cloned the cDNA of rabbit MK, which showed a strongly conserved sequence in mammals. The balloon injury induced MK expression, with the maximum level occurring 7–14 days after angioplasty, in the rabbit carotid artery. Two antisense ODNs suppressed the production of MK in a rabbit kidney cell line, RK13 cells, one of which was then transfected into the arterial wall by means of lipofection immediately after balloon treatment. The antisense ODN suppressed MK induction in vivo and consequently suppressed neointima formation to 60% of the control level. These results suggest that MK is a candidate molecular target for the therapy for vascular restenosis.

molecular target; phosphorothioate; vascular restenosis



Address for reprint requests and other correspondence: K. Kadomatsu or T. Muramatsu, Dept. of Biochemistry, Nagoya Univ. School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan (E-mail: kkadoma{at}med.nagoya-u.ac.jp or tmurama{at}med.nagoya-u.ac.jp)




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T. Kosugi, Y. Yuzawa, W. Sato, H. Kawai, S. Matsuo, Y. Takei, T. Muramatsu, and K. Kadomatsu
Growth Factor Midkine Is Involved in the Pathogenesis of Diabetic Nephropathy
Am. J. Pathol., January 1, 2006; 168(1): 9 - 19.
[Abstract] [Full Text] [PDF]




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