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Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries

Mandinov, L. (author)
Maine Medical Center, Scarborough, Maine, USA
L. Moodie, K. (author)
Dartmouth-Hitchcock Medical Center, Hanover, NH, USA
Mandinova, A. (author)
Maine Medical Center, Scarborough, Maine, USA
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Zhuang, Z. (author)
Dartmouth-Hitchcock Medical Center, Hanover, NH, USA
Redican, F. (author)
Dartmouth-Hitchcock Medical Center, Hanover, NH, USA
Baklanov, D. (author)
Dartmouth-Hitchcock Medical Center, Hanover, NH, USA
Lindner, V. (author)
Maine Medical Center, Scarborough, Maine, USA
Maciag, T. (author)
Maine Medical Center, Scarborough, Maine, USA
Simons, M. (author)
Dartmouth-Hitchcock Medical Center, Hanover, NH, USA
de Muinck, Ebo D. (author)
Maine Medical Center, Scarborough, Maine, USA
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 (creator_code:org_t)
American Physiological Society, 2006
2006
English.
In: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 291:6, s. H2692-H2697
Related links:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Stress-induced release of IL-1 alpha 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 less than 0.05), percent stenosis diameter was 39% less in TTM-treated animals (27.1 +/- 16.6% vs. 44.5 +/- 16.1%, P less than 0.05), minimal lumen area by IVUS was 60% larger in TTM-treated animals (4.27 +/- 1.56 vs. 2.67 +/- 1.19 mm(2), P less than 0.05), and neointimal volume by histomorphometry was 37% less in TTM-treated animals (34.9 +/- 11.5 vs. 55.2 +/- 19.6 mm(3), P less than 0.05). We conclude that systemic copper chelation with a clinically approved chelator significantly inhibits in-stent restenosis.

Keyword

inflammation; stent

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