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.
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