Inhibition of in-stent restenosis by oral copper chelation in porcine coronary arteries
2006 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 291, no 6, H2692-H2697 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
American Physiological Society , 2006. Vol. 291, no 6, H2692-H2697 p.
Medical and Health Sciences Engineering and Technology
IdentifiersURN: urn:nbn:se:liu:diva-99964DOI: 10.1152/ajpheart.00148.2006ISI: 000241855900021OAI: oai:DiVA.org:liu-99964DiVA: diva2:659135