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:
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