Macejak D G, Lin H, Webb S, Chase J, Jensen K, Jarvis T C, Leiden J M, Couture L
Ribozyme Pharmaceuticals, Inc., Boulder, Colorado 80301, USA.
J Virol. 1999 Sep;73(9):7745-51. doi: 10.1128/JVI.73.9.7745-7751.1999.
Smooth muscle cell (SMC) proliferation is an important component of restenosis in response to injury after balloon angioplasty. Inhibition of proliferation in vivo can limit neointima hyperplasia in animal models of restenosis. Ribozymes against c-myb mRNA have been shown to be effective inhibitors of SMC proliferation in vitro. The effectiveness of adenovirus as a gene therapy vector in animal models of restenosis is well documented. In order to test the utility of ribozymes to inhibit SMC proliferation by a gene therapy approach, recombinant adenovirus expressing ribozymes against c-myb mRNA was generated and tested both in vitro and in vivo. This adenovirus ribozyme vector is shown to inhibit SMC proliferation in culture and neointima formation in a rat carotid artery balloon injury model of restenosis.
平滑肌细胞(SMC)增殖是球囊血管成形术后损伤引起再狭窄的一个重要组成部分。体内增殖抑制可限制再狭窄动物模型中的新生内膜增生。针对c-myb mRNA的核酶已被证明是体外SMC增殖的有效抑制剂。腺病毒作为基因治疗载体在再狭窄动物模型中的有效性已有充分记录。为了通过基因治疗方法测试核酶抑制SMC增殖的效用,构建了表达针对c-myb mRNA的核酶的重组腺病毒,并在体外和体内进行了测试。这种腺病毒核酶载体在培养中可抑制SMC增殖,并在大鼠颈动脉球囊损伤再狭窄模型中抑制新生内膜形成。