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

Steger CM, Bonaros N, Rieker R, Bonatti J, Schachner T (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Experimental and Molecular Pathology Elsevier

Book Volume: 105

Pages Range: 1-9

Journal Issue: 1

DOI: 10.1016/j.yexmp.2018.05.003

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 oligonucleotide treatment in a mouse model of vein graft disease including the significant reduction of neointimal, media and total vessel wall thickness with a significantly lower percentage of SMA positive cells, elastic fibres and acid mucopolysaccharides in the neointima and media, a decreased vascularization, and a lower expression of PDGFR ß, MMP-9 and VEGF-A positive cells throughout the whole vein graft wall.

Authors with CRIS profile

Ralf Rieker Institute of Pathology

Involved external institutions

Landeskrankenhaus Feldkirch AT Austria (AT) Medizinische Universität Innsbruck AT Austria (AT) Cleveland Clinic Abu Dhabi LLC AE United Arab Emirates (AE)

How to cite

APA:

Steger, C.M., Bonaros, N., Rieker, R., Bonatti, J., & Schachner, T. (2018). 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, 105(1), 1-9. https://doi.org/10.1016/j.yexmp.2018.05.003

MLA:

Steger, Christina Maria, et al. "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 105.1 (2018): 1-9.

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