Published online before print May 12, 2003, doi: 10.1161/01.CIR.0000074042.19447.B1
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(Circulation. 2003;107:2551.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Intramural Delivery of Recombinant Apolipoprotein A-IMilano/Phospholipid Complex (ETC-216) Inhibits In-Stent Stenosis in Porcine Coronary Arteries
From the Vascular Physiology and Thrombosis Research Laboratory of the Atherosclerosis Research Center (S.K., V.R., R.S., B.A., V.T.T., K.-Y.C., B.C., J.M., P.K.S.), the Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, Calif; and Esperion Therapeutics, Inc (C.L.B., J.J.), Ann Arbor, Mich.
Correspondence to Sanjay Kaul, MD, Division of Cardiology, Rm 5314, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail kaul{at}cshs.org
Background— We have previously demonstrated vasculoprotective effects after repeated intravenous administration of recombinant apolipoprotein A-IMilano (apoA-Im)/phospholipid complex. In this study, we sought to determine the effects of local recombinant apoA-Im/1-palmitoyl,2-oleoyl phosphatidylcholine complex (ETC-216) delivered intramurally via the Infiltrator catheter on luminal narrowing in a porcine coronary artery stent overstretch injury model.
Methods and Results— In twelve domestic swine (
25 kg), two arteries each were infiltrated with 0.4 mL ETC-216 (14 mg/mL) or vehicle control immediately before deployment of GFX stents (stent:artery ratio=1.3:1). Animals were euthanized at day 28, and evaluation by QCA revealed a significant improvement in mean lumen loss index with ETC-216 treatment (21±22% versus 43±13% lumen loss; P=0.01). Histomorphometric analysis showed that ETC-216 treatment significantly reduced the intimal area (6.7±1.5 versus 5.2±1.4 mm2, -22%; P=0.02) and the stenosis index (0.76±0.15 versus 0.59±0.15; P=0.01), and increased the lumen area (2.1±1.4 versus 3.7±1.8 mm2, +76%; P=0.02). Regression analysis showed significant differences in lumen area (P=0.004), neointimal area (P=0.003), stenosis index (P=0.001), and neointimal thickness (P=0.003) adjusted for injury score in favor of ETC-216.
Conclusions— A single intramural administration of ETC-216 significantly inhibited injury-induced luminal narrowing in the porcine stent overstretch model through reduction of intimal hyperplasia. These data show that local intracoronary delivery of ETC-216 may be useful to prevent restenosis after coronary stenting.
Key Words: lipoproteins • restenosis • stents
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