Abstract 17425: Local Anti-angiogenic Gene Therapy Reduces Vasa-vasorum Growth and In-stent Restenosis in a Preclinical Model of Restenosis
In-stent restenosis (ISR) remains a key limitation to endovascular revascularization therapies. The growth of vasa vasorum into the lesion from the adventitia has been suggested as an accelerator for the process of ISR and Vascular Endothelial Growth Factor (VEGF) is the key mediator of angiogenesis. We studied the therapeutic potential of local anti-angiogenic therapy for ISR by utilizing soluble VEGF receptors that act as decoys and reduce the amount of free VEGF in the tissue.
67 hyperlipidemic WHHL rabbit aortas were denuded of endothelium. Six weeks later a section of the aortic wall was injected with 1.5x10e10 pfu adenovirus encoding soluble VEGF Receptor 1 (sVEGFR1), sVEGFR2, sVEGFR3 or control LacZ using a needle catheter. A bare metal stent was implanted on the same segment. Control angiographies and euthanasia were performed on d6, d14, d42 and d90 followed by histological analyses.
Gene transfer efficacy was assessed at d6 with LacZ controls and found to be localized in the adventitia. At d14 the sVEGFR2 treated group had significantly fewer (per mm2) and smaller capillaries compared to control (p<0.005) in the adventitia. There were no differences in the size and number of vasa-vasorum at later time points. The intima-media ratio (IMR) for sVEGFR2 group was 39.0% smaller that control (p<0.05). The IMR was not significantly lower in the treated arteries compared to LacZ at the later time point of d90.
Local anti-angiogenic gene delivery was able to limit the growth on vasa-vasorum vessels in the adventitial tissue two weeks after treatment. This resulted in an attenuated rate of in-stent restenosis at a later time point of d42. Possibly due to the short expression time of the adenovirus mediated treatment, the results were no longer clear 90 days after treatment. However, targeting lesion revascularization might be a feasible option in the future when battling in-stent restenosis.
- © 2013 by American Heart Association, Inc.