Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Dong Wang - , Universität Hamburg (Autor:in)
  • Tobias Deuse - , Universität Hamburg (Autor:in)
  • Mandy Stubbendorff - , Universität Hamburg (Autor:in)
  • Ekaterina Chernogubova - , Karolinska Institutet (Autor:in)
  • Reinhold G. Erben - , Veterinärmedizinische Universität Wien (Autor:in)
  • Suzanne M. Eken - , Karolinska Institutet (Autor:in)
  • Hong Jin - , Karolinska Institutet (Autor:in)
  • Yuhuang Li - , Karolinska Institutet (Autor:in)
  • Albert Busch - , Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Karolinska Institutet (Autor:in)
  • Christian H. Heeger - , Asklepios Klinik St. Georg (Autor:in)
  • Boris Behnisch - , Translumina GmbH (Autor:in)
  • Hermann Reichenspurner - , Universität Hamburg (Autor:in)
  • Robert C. Robbins - , Stanford University (Autor:in)
  • Joshua M. Spin - , Department of Veterans Affairs, Stanford University (Autor:in)
  • Philip S. Tsao - , Department of Veterans Affairs, Stanford University (Autor:in)
  • Sonja Schrepfer - , Universität Hamburg, Stanford University (Autor:in)
  • Lars Maegdefessel - , Karolinska Institutet (Autor:in)

Abstract

OBJECTIVE: Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) because of myointimal hyperplasia remains a major complication.

APPROACH AND RESULTS: We investigated the regulatory role of microRNAs in myointimal hyperplasia/ISR, using a humanized animal model in which balloon-injured human internal mammary arteries with or without stenting were transplanted into Rowett nude rats, followed by microRNA profiling. miR-21 was the only significantly upregulated candidate. In addition, miR-21 expression was increased in human tissue samples from patients with ISR compared with coronary artery disease specimen. We systemically repressed miR-21 via intravenous fluorescein-tagged-locked nucleic acid-anti-miR-21 (anti-21) in our humanized myointimal hyperplasia model. As expected, suppression of vascular miR-21 correlated dose dependently with reduced luminal obliteration. Furthermore, anti-21 did not impede reendothelialization. However, systemic anti-miR-21 had substantial off-target effects, lowering miR-21 expression in liver, heart, lung, and kidney with concomitant increase in serum creatinine levels. We therefore assessed the feasibility of local miR-21 suppression using anti-21-coated stents. Compared with bare-metal stents, anti-21-coated stents effectively reduced ISR, whereas no significant off-target effects could be observed.

CONCLUSION: This study demonstrates the efficacy of an anti-miR-coated stent for the reduction of ISR.

Details

OriginalspracheEnglisch
Seiten (von - bis)1945-1953
Seitenumfang9
FachzeitschriftArteriosclerosis, thrombosis, and vascular biology
Jahrgang35
Ausgabenummer9
PublikationsstatusVeröffentlicht - 28 Sept. 2015
Peer-Review-StatusJa

Externe IDs

Scopus 84940398432

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • coronary restenosis, hyperplasia, microRNAs, rats, stents