Gene therapy with antisense oligonucleotides silencing c-myc reduces neointima formation and vessel wall thickness in a mouse model of vein graft disease

Experimental and Molecular Pathology
Christina Maria StegerThomas Schachner

Abstract

Gene therapy for avoiding intimal hyperplasia of vein grafts after coronary artery bypass grafting is still discussed controversially. A promising application of gene therapy in vein grafts is the use of antisense oligonucleotides to block the expression of genes encoding cell cycle regulatory proteins in vascular smooth muscle cells. C-myc, either directly or by regulating the expression of other proteins, controls cell proliferation, apoptosis and cell survival, tissue remodeling, angiogenesis, cell metabolism, production of inflammatory and anti-inflammatory cytokines, and also participates in cell transformation. Forty C57BL/6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a previously described cuff technique. Twenty mice received periadventitial administration of antisense oligonucleotides directed against c-myc (treatment group), the other twenty mice received no treatment (control group). All vein grafts were harvested two weeks after surgery, dehydrated, wax embedded, cut into slides of 2 μm thickness, stained and histologically and immunohistochemically examined under light microscope. In our study, we could show the promising effects of antisense ...Continue Reading

Citations

May 14, 2020·Polymers·Viktor Korzhikov-VlakhTatiana B Tennikova

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