Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries
| Autor: | Michael Simons, Dmitri V. Baklanov, Karen L Moodie, F. Redican, Zhen W. Zhuang, Volkhard Lindner, Anna Mandinova, E D de Muinck, Thomas Maciag, Lazar Mandinov |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Swine Physiology medicine.medical_treatment Pharmacology Coronary Angiography Coronary Restenosis Restenosis Physiology (medical) Internal medicine medicine Animals Fibroblast Ultrasonography Interventional Chelating Agents Molybdenum Neointimal hyperplasia business.industry Ceruloplasmin Stent Copper Chelation medicine.disease Coronary Vessels Chelation Therapy Coronary arteries Disease Models Animal medicine.anatomical_structure Circulatory system Cardiology Stents Tunica Intima Cardiology and Cardiovascular Medicine business Copper Intracellular |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 291:H2692-H2697 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Stress-induced release of IL-1α and fibroblast growth factor-1 is dependent on intracellular copper and is a major driver of neointimal hyperplasia. Therefore, we assessed the effect of tetrathiomolybdate (TTM), a clinically proven copper chelator, on in-stent restenosis. Nine pigs were treated with TTM (5 mg/kg po) twice daily for 2 wk before stent implantation and for 4 wk thereafter, and nine pigs served as controls. In-stent restenosis was assessed by quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), and histomorphometry. Serum ceruloplasmin activity was used as a surrogate marker of copper bioavailability. In TTM-treated animals, ceruloplasmin dropped 70 ± 10% below baseline levels. Baseline characteristics were comparable in TTM-treated and control animals. At 4-wk follow-up, all parameters relevant to in-stent restenosis were significantly reduced in TTM-treated animals: minimal lumen diameter by QCA was 2.03 ± 0.57 and 1.47 ± 0.45 mm in TTM-treated and control animals, respectively ( P < 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 ± 16.6% vs. 44.5 ± 16.1%, P < 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 ± 1.56 vs. 2.67 ± 1.19 mm2, P < 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 ± 11.5 vs. 55.2 ± 19.6 mm3, P < 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|