Nature Medicine
3, 900 - 903 (1997)
doi:10.1038/nm0897-900
Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase oligonucleotideJun-Ichi Suzuki1, Mitsuaki Isobe1, 5, Ryuichi Morishita2, Motokuni Aoki2, Shiro Horie1, Yoshio Okubo1, Yasufumi Kaneda4, Yoshiki Sawa4, Hikaru Matsuda4, Toshio Ogihara2
& Morie Sekiguchi1
1First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390, Japan
2Department of Geriatric Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan
3Institute for Cellular and Molecular Biology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan
4First Department of Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan
5Correspondence should be addressed to M.I. Graft coronary arteriosclerosis, which limits the long-term survival of allograft recipients, is characterized by diffuse intimal thickening composed of proliferative smooth muscle cells1,2. We observed that messenger RNA of the cell cycle regulatory enzyme cyclin-dependent kinase (cdk) 2 kinase, which mediates smooth muscle cell proliferation, was elevated in the thickened intima of coronary arteries of murine heterotopic cardiac allo-grafts. We studied the effects of antisense phosphorothioate oligodeoxynucleotide (ODN) against this enzyme using gene transfer mediated by a hemagglutinating virus of Japan (HVJ)−liposome complex intraluminally delivered to inhibit the intimal hyperplasia. At 30 days after transplantation, antisense cdk2 kinase ODN treatment had dramatically inhibited neointi-mal formation in the allografts. Expression of vascular cell adhesion molecule-1 was also suppressed by antisense cdk2 kinase. However, these effects were not observed in the sense or scrambled ODN-treated allografts. Thus, an intraluminal administration of antisense ODN directed to a specific cell cycle regulatory gene can inhibit neointimal formation after cardiac transplantation.
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