Abstract 18166: Increasing Endothelialization of BMS and DES With Intra-arterial AdVEGF-A Gene Therapy in Porcine Coronary Arteries

Abstract

We aimed to increase stent endothelialization with gene therapy known to promote endothelial proliferation. In addition, we evaluated OCT and angioscopy imaging as tools for detecting endothelium with comparison to robust ex-vivo analyses including scanning electron microscopy (SEM), multiphoton microscopy and immunohistology. 24 stents, BMS and DES, were implanted into naïve porcine coronary arteries and received either AdVEGF-A or control AdLacZ gene therapy with a porous drug delivery catheter. Stents were imaged in-vivo with angiography, OCT and angioscopy immediately after stenting and one week and two weeks after stenting and gene therapy. At d14 the stents were collected for histology, multi-photon microscopy and scanning electron microscopy for assessment of endothelialization. Strut coverage was analyzed from SEM images and graded 0 (no coverage) to 3 (fully covered). Angioscopy pullbacks were analyzed for thrombus in the stented artery and graded similarly 0 (no thrombus) to 3 (occlusive thrumbus). Initial SEM analyses from stented arteries two weeks after intervention showed increased strut coverage with BMS after VEGF-A gene therapy compared to control LacZ (2.8±0.4 vs. 1.8±0.4, p=0.0031, respectively, a) and b) in figure). Gene therapy did not change strut coverage in DES with stent coverage of 1.6±0.5 and 1.8±0.4, p=NS, AdLacZ and AdVEGF-A respectively. Angioscopic thrombus formation was low in all groups with a trend towards less thrombi on BMS groups (0.2±0.4 and 0.3±0.5 in AdLacZ and AdVEGF-A) compared to DES (0.8±0.8 and 0.8±0.7 in AdLacZ and AdVEGF, c) in figure with red thrombus at 4 o'clock). AdVEGF-A treatment at the time of stenting increased coverage of BMS but did not improve healing of DES two weeks after stenting. Likely the strong cytotoxic drugs in DES hamper stent healing even with local supraphysiological growth factor concentrations. Angioscopy may be useful in assessment of arterial healing after treatment with a coronary stent.