on May 12, 2003
Published online before print May 12, 2003, doi: 10.1161/01.CIR.0000074042.19447.B1
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 29, 2003
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. * To whom correspondence should be addressed. 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 ( 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.
Revised on March 20, 2003
Accepted on April 11, 2003
Intramural Delivery of Recombinant Apolipoprotein A-IMilano/Phospholipid Complex (ETC-216) Inhibits In-Stent Stenosis in Porcine Coronary Arteries
Sanjay Kaul MD*,
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.
Key words: lipoproteins • restenosis • stents
This article has been cited by other articles:
 |
|
 |
|
  F. M. Sacks, L. L. Rudel, A. Conner, H. Akeefe, G. Kostner, T. Baki, G. Rothblat, M. de la Llera-Moya, B. Asztalos, T. Perlman, et al. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo J. Lipid Res., May 1, 2009; 50(5): 894 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Parolini, M. Marchesi, P. Lorenzon, M. Castano, E. Balconi, L. Miragoli, L. Chaabane, A. Morisetti, V. Lorusso, B. J. Martin, et al. Dose-related effects of repeated ETC-216 (recombinant apolipoprotein A-I Milano/1-palmitoyl-2-oleoyl phosphatidylcholine complexes) administrations on rabbit lipid-rich soft plaques: in vivo assessment by intravascular ultrasound and magnetic resonance imaging. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1098 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ibanez, G. Vilahur, G. Cimmino, W. S. Speidl, A. Pinero, B. G. Choi, M. U. Zafar, C. G. Santos-Gallego, B. Krause, L. Badimon, et al. Rapid change in plaque size, composition, and molecular footprint after recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic resonance imaging study in an experimental model of atherosclerosis. J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1104 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Masson, J.-P. Pais de Barros, Z. Zak, T. Gautier, N. Le Guern, M. Assem, J. W. Chisholm, J. R. Paterniti Jr., and L. Lagrost Human apoA-I expression in CETP transgenic rats leads to lower levels of apoC-I in HDL and to magnification of CETP-mediated lipoprotein changes J. Lipid Res., February 1, 2006; 47(2): 356 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gupta, C. R. White, S. Handattu, D. W. Garber, G. Datta, M. Chaddha, L. Dai, S. H. Gianturco, W. A. Bradley, and G.M. Anantharamaiah Apolipoprotein E Mimetic Peptide Dramatically Lowers Plasma Cholesterol and Restores Endothelial Function in Watanabe Heritable Hyperlipidemic Rabbits Circulation, June 14, 2005; 111(23): 3112 - 3118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Marchesi, E. A. Booth, T. Davis, C. L. Bisgaier, and B. R. Lucchesi Apolipoprotein A-IMilano and 1-Palmitoyl-2-oleoyl Phosphatidylcholine Complex (ETC-216) Protects the in Vivo Rabbit Heart from Regional Ischemia-Reperfusion Injury J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 1023 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaul, B. Coin, A. Hedayiti, J. Yano, B. Cercek, K.-Y. Chyu, and P. K. Shah Rapid reversal of endothelial dysfunction in hypercholesterolemic apolipoprotein E-null mice by recombinant apolipoprotein A-IMilano-phospholipid complex J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1311 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Rossoni, M. Gomaraschi, F. Berti, C. R. Sirtori, G. Franceschini, and L. Calabresi Synthetic High-Density Lipoproteins Exert Cardioprotective Effects in Myocardial Ischemia/Reperfusion Injury J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 79 - 84. [Abstract] [Full Text] [PDF]
|
|