Abe J, Zhou W, Taguchi J, Takuwa N, Miki K, Okazaki H, Kurokawa K, Kumada M, Takuwa Y
Department of Cardiovascular Biology, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1994 Jan 14;198(1):16-24. doi: 10.1006/bbrc.1994.1003.
Deendothelializing balloon injury of rat carotid artery results in progressive intimal smooth muscle cell accumulation and luminal stenosis over 14 days after injury. We have found transient rises (approximately 3-fold maximal increases over the uninjured control value) of the kinase activities of both cdc2 and cdk2, key molecules for cell cycle progression, in the injured carotid artery along with the development of intimal proliferation. The topical application of the antisense, but not the sense, cdc2 and cdk2 phosphorothioate oligodeoxynucleotides dissolved in F127 pluronic gel around the freshly injured artery resulted in reductions of the intimal smooth muscle cell accumulation by 47% and 55% respectively, as estimated by an intimal to medial cross-sectional area ratio, with concomitant decreases in cdc2 and cdk2 kinase activities. These results indicate that both cdc2 and cdk2 kinases are involved in intimal smooth muscle cell accumulation after balloon angioplasty and suggest a potential usefulness of the antisense cdc2 and cdk2 oligonucleotide therapy for arterial stenosis.
大鼠颈动脉去内皮球囊损伤会导致损伤后14天内内膜平滑肌细胞逐渐积累和管腔狭窄。我们发现在损伤的颈动脉中，随着内膜增殖的发展，细胞周期进程的关键分子cdc2和cdk2的激酶活性出现短暂升高（比未损伤对照值最大增加约3倍）。将溶解于F127普朗尼克凝胶中的反义而非正义cdc2和cdk2硫代磷酸酯寡脱氧核苷酸局部应用于刚损伤的动脉周围，通过内膜与中膜横截面积比估计，内膜平滑肌细胞积累分别减少了47%和55%，同时cdc2和cdk2激酶活性降低。这些结果表明，cdc2和cdk2激酶均参与球囊血管成形术后内膜平滑肌细胞的积累，并提示反义cdc2和cdk2寡核苷酸疗法对动脉狭窄可能具有潜在的治疗作用。
