Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase oligonucleotide
Author: ["Jun-Ichi Suzuki","Mitsuaki Isobe","Ryuichi Morishita","Motokuni Aoki","Shiro Horie","Yoshio Okubo","Yasufumi Kaneda","Yoshiki Sawa","Hikaru Matsuda","Toshio Ogihara","Morie Sekiguchi"]
Publication: Nature Medicine
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Abstract
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.
Cite this article
Suzuki, JI., Isobe, M., Morishita, R. et al. Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase oligonucleotide. Nat Med 3, 900–903 (1997). https://doi.org/10.1038/nm0897-900
