Possible uses of gene therapy in reducing coronary restenosis

Abstract

Four overlapping stages occur in the development of restenosis as described in animal models. The inflammatory and thrombotic phases begin at the time of injury and are maximal hours later. These are followed by a proliferative phase, with the highest division activity of smooth muscle cells about seven days after injury. Finally, there is matrix formation from one week onwards.1 As part of these processes, extracellular growth factors bind to cell surface receptors and can initiate the cascade required for signal transduction that leads eventually to cell division. Proto-oncogenes in the normal growth–regulatory pathway are stimulated by these factors, are transiently switched on, and, together with other cell cycle related genes, regulate cell division. Cell proliferation in restenosis may also result from a reduction in inhibitory cell cycle controlling factors.