Kitamoto Shiro, Egashira Kensuke
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Expert Rev Cardiovasc Ther. 2003 Sep;1(3):393-400. doi: 10.1586/14779072.1.3.393.
Recent studies have revealed that increased expression of monocyte chemoattractant protein (MCP)-1 plays a central role in the pathogenesis of cardiovascular diseases. 7ND is the amino-terminal deletion mutant of human MCP-1 and works as a dominant negative inhibitor of MCP-1. We devised a new strategy of anti-MCP-1 gene therapy by transfecting the 7ND gene into skeletal muscles. 7ND gene transfection suppressed arteriosclerotic changes induced by chronic inhibition of nitric oxide synthesis in rats and inhibited the development, progression and destabilization of atherosclerosis in apolipoprotein E knockout mice. This strategy also reduced restenosis after balloon injury in rats, rabbits and monkeys, and reduced neointimal formation after stent implantation in rabbits and monkeys. This new strategy can be a useful and feasible gene therapy against MCP-1 related cardiovascular diseases.
最近的研究表明，单核细胞趋化蛋白（MCP）-1表达增加在心血管疾病的发病机制中起核心作用。7ND是人MCP-1的氨基末端缺失突变体，可作为MCP-1的显性负性抑制剂。我们通过将7ND基因转染到骨骼肌中，设计了一种新的抗MCP-1基因治疗策略。7ND基因转染抑制了大鼠一氧化氮合成慢性抑制诱导的动脉硬化变化，并抑制了载脂蛋白E基因敲除小鼠动脉粥样硬化的发生、发展和不稳定。该策略还减少了大鼠、兔子和猴子球囊损伤后的再狭窄，以及兔子和猴子支架植入后的新生内膜形成。这种新策略可能是一种针对MCP-1相关心血管疾病的有用且可行的基因治疗方法。
