A novel CX3CR1 antagonist eluting stent reduces stenosis by targeting inflammation
| Autor: | Stefan Pierrou, Wisam Khider, Birgitta M. Gleeson, Erika Cavallin, Kenneth Martin, Arun H.S. Kumar, Mohammed T. Ali, Carl J. Vaughan, Noel M. Caplice, Elizebeth C. Turner, William L. McPheat, Chien-Ling Huang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Materials science Swine medicine.medical_treatment Myocytes Smooth Muscle Biophysics Anti-Inflammatory Agents CX3C Chemokine Receptor 1 Bioengineering Inflammation Pharmacology Biomaterials chemistry.chemical_compound Coated Materials Biocompatible Polylactic Acid-Polyglycolic Acid Copolymer Internal medicine medicine Animals cardiovascular diseases Lactic Acid PI3K/AKT/mTOR pathway Cell Proliferation Neointimal hyperplasia Monocyte Coronary Stenosis Stent Drug-Eluting Stents equipment and supplies medicine.disease Coronary Vessels PLGA Stenosis surgical procedures operative medicine.anatomical_structure chemistry Mechanics of Materials Drug-eluting stent Ceramics and Composites Cardiology Female Receptors Chemokine medicine.symptom Polyglycolic Acid |
| Zdroj: | Biomaterials. 69 |
| ISSN: | 1878-5905 |
| Popis: | We evaluated the therapeutic efficacy of a novel drug eluting stent (DES) inhibiting inflammation and smooth muscle cell (SMC) proliferation. We identified CX3CR1 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 CX3CR1 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 μM/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 CX3CL1 in a dose dependent manner. AZ1220 eluted from polymer coated stents in an ex vivo flow system retained bioactivity in inhibiting monocyte attachment to CX3CL1. At 4 weeks following deployment, AZ1220 eluting stents significantly reduced (∼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-CX3CR1 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. |
| Databáze: | OpenAIRE |
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