Inhibition of intimal hyperplasia via local delivery of vascular endothelial growth factor cDNA nanoparticles in a rabbit model of restenosis induced by abdominal aorta balloon injury.

Abstract

In-stent restenosis (ISR) is one of the major factors affecting long-term outcomes of percutaneous coronary interventions. Vascular endothelial growth factor (VEGF) has been hypothesized to have a positive role in preventing ISR, however, this remains controversial. The aim of the present study was to assess whether nanoparticles can be used to deliver VEGF to injured arteries and whether this is beneficial in preventing restenosis. New Zealand White rabbits were randomly divided into a control group, an empty nanoparticles group and a VEGF nanoparticles group (n=6 in each group). Polylactic-polyglycolic acid VEGF nanoparticles were prepared using a phacoemulsification method. A rabbit model of restenosis was established following abdominal aorta balloon injury, and VEGF gene nanoparticles, empty nanoparticles or normal saline were delivered locally at the site of injury via a GENIE Catheter™ perfusion balloon. Intimal proliferation determination and immunohistochemistry analysis were performed at day 28 following arterial injury. Compared with the control and empty nanoparticle groups, the neointima area (0.49±0.09, 0.48±0.08 and 0.19±0.11 mm2, respectively; P<0.001) and proliferation index (0.32±0.03, 0.32±0.05 and 0.13±0.06, respectively; P<0.001) were significantly lower in the VEGF nanoparticles group. In addition, in the VEGF nanoparticles group, the immunoreactivity of α-actin and proliferating cell nuclear antigen were significantly lower (P≤0.001), while the immunoreactivity of VEGF was higher (P=0.01). Therefore, the results revealed that local delivery of VEGF gene nanoparticles reduced intimal thickening and cell proliferation following abdominal aorta balloon injury in a rabbit model, demonstrating the efficacy of this therapy against restenosis.