Peer-Reviewed Journal Details
Mandatory Fields
Ali, MT,Martin, K,Kumar, AHS,Cavallin, E,Pierrou, S,Gleeson, BM,McPheat, WL,Turner, EC,Huang, CL,Khider, W,Vaughan, C,Caplice, NM
2015
November
Biomaterials
A novel CX(3)CR1 antagonist eluting stent reduces stenosis by targeting inflammation
Validated
WOS: 12 ()
Optional Fields
CX(3)CR1 Drug eluting stents In-stent stenosis Stent re-endothelization SMOOTH-MUSCLE-CELLS BARE-METAL STENTS CORONARY-ARTERY NEOINTIMAL HYPERPLASIA RECEPTOR CX3CR1 RESTENOSIS FRACTALKINE INJURY ATHEROSCLEROSIS IMPLANTATION
69
22
29
We evaluated the therapeutic efficacy of a novel drug eluting stent (DES) inhibiting inflammation and smooth muscle cell (SMC) proliferation. We identified CX(3)CR1 as a targetable receptor for prevention of monocyte adhesion and inflammation and in-stent neointimal hyperplasia without interfering with stent re-endothelization. Efficacy of AZ12201182 (AZ1220), a CX(3)CR1 antagonist was evaluated in inhibition of monocyte attachment in vitro. A prototype AZ1220 eluting PLGA-based polymer coated stent developed with an optimal elution profile and dose of 1 mu M/stent was tested over 4 weeks in a porcine model of coronary artery stenting. Polymer coated stents without AZ1220 and bare metal stents were used as controls. AZ1220 inhibited monocyte attachment to CX(3)CL1 in a dose dependent manner. AZ1220 eluted from polymer coated stents in an ex vivo flow system retained bioactivity in inhibiting monocyte attachment to CX(3)CL1. At 4 weeks following deployment, AZ1220 eluting stents significantly reduced (similar to 60%) in-stent stenosis compared to both bare metal and polymer only coated stents and markedly reduced peri-stent inflammation and monocyte/macrophage accumulation without affecting re-endothelization. Anti-CX(3)CR1 drug eluting stents potently inhibited in-stent stenosis and may offer an alternative to mTOR targeting by current DES, specifically inhibiting polymer-induced inflammatory response and SMC proliferation, while retaining an equivalent re-endothelization response to bare metal stents. (C) 2015 Elsevier Ltd. All rights reserved.
10.1016/j.biomaterials.2015.07.059
Grant Details