Author + information
- Received September 28, 1996
- Revision received January 7, 1997
- Accepted January 28, 1997
- Published online May 1, 1997.
- Eric Van Belle, MDA,
- Fermin O Tio, MDB,
- Donghui Chen, MDA,
- Luc Maillard, MDA,
- Dongfen Chen, MDA,
- Marianne Kearney, BSA and
- Jeffrey M Isner, MD, FACCA,* ()
- ↵*Dr. Jeffrey M. Isner, St. Elizabeth’s Medical Center, 736 Cambridge Street, Boston, Massachusetts 02135.
Objectives. This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis.
Background. Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility.
Methods. Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected.
Results. Stent endothelialization was accelerated by phVEGF165gene transfer (87.38 ± 5.06% vs. 33.13 ± 9.73% [mean ± SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 ± 2.4% vs. 32.7 ± 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 ± 0.09 vs. 1.44 ± 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits.
Conclusions. These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thombus and obstruction due to intimal thickening.
(J Am Coll Cardiol 1997;29:1371–9)
☆ This study was supported in part by Grants HL02824 and HL 53354 (Dr. Isner) from the National Heart, Lung, Blood Institute, National Institutes of Health, Bethesda, Maryland; the E. L. Weigand Foundation, Reno, Nevada; and the John and Cora Davis Foundation, Washington, D.C.
- Received September 28, 1996.
- Revision received January 7, 1997.
- Accepted January 28, 1997.
- The American College of Cardiology