Intramural delivery of recombinant apolipoprotein A-IMilano/phospholipid complex (ETC-216) inhibits in-stent stenosis in porcine coronary arteries.
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.


RESULTS
In twelve domestic swine ( approximately 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.
Vascular Physiology and Thrombosis Research Laboratory of the Atherosclerosis Research Center, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA. kaul@cshs.org
Sanjay
S
Kaul
Vladimir
V
Rukshin
Raul
R
Santos
Babak
B
Azarbal
Charles L
CL
Bisgaier
Jan
J
Johansson
Vivian T
VT
Tsang
Kuang-Yuh
KY
Chyu
Bojan
B
Cercek
James
J
Mirocha
Prediman K
PK
Shah
D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D007269:Injections, Intra-Arterial; D046911:Macromolecular Substances; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D010743:Phospholipids / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D015607:Stents / Q000009:adverse effects; D013552:Swine; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects
D016632:Apolipoprotein A-I; C474616:ETC216; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D010743:Phospholipids; D011994:Recombinant Proteins; C080631:apolipoprotein A-I Milano