[Gene therapy in interventional coronary interventions].
BACKGROUND
30-50% of patients develop restenosis after PTCA. While most pharmacologic strategies fail to reduce restenosis rate, only implantation of stents and brachytherapy have shown to improve long-term outcome of coronary angioplasty significantly.
With expanding knowledge of the process resulting in activation and inhibition of gene expression after angioplasty, a number of studies showed by inhibiting overexpression of some genes or overexpressing down-regulated other genes significant and extensive reduction of neointimal hyperplasia in different angioplasty models. Until now there have no results of clinical trials to reduce restenosis by gene therapy been published.
Gene therapy offer the opportunity to specifically inhibit activation of genes resulting in restenosis. However, until now no single gene responsible for the restenosis process could be identified. Several strategies interfering with gene expression at different levels, such as ligand-receptor binding, cell cycle regulation or induction of apoptosis have reduced restenosis in animal experimental models. This variety of successful interventions supports the concept of a redundancy in signaling pathways leading to vessel wall proliferatioin and restenosis. Restenosis rates have been reduced by stents and brachytherapy. The first results of trials with a coated stent eluting an immunosuppressant suggest a further reduction. These data raise the question whether a clinically successful and safe specific gene therapy can be developed before the problem of restenosis is largely solved by unspecific inhibition of proliferation.
Buchwald
Arnd B
AB
Abteilung Kardiologie und Pneumologie, Herzzentrum Göttingen, Universitätsklinik, Germany. buchwald@med.uni-goettingen.de
D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D001918:Brachytherapy; D020099:Coated Materials, Biocompatible; D003131:Combined Modality Therapy; D023903:Coronary Restenosis / Q000235:genetics / Q000628:therapy*; D023921:Coronary Stenosis / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D017063:Outcome Assessment, Health Care; D015607:Stents
D020099:Coated Materials, Biocompatible; D007166:Immunosuppressive Agents