The formation of an anti-restenotic/anti-thrombotic surface by immobilization of nitric oxide synthase on a metallic carrier

M. Alagem-Shafir, E. Kivovich, I. Tzchori, N. Lanir, M. Falah, M. Y. Flugelman, U. Dinnar, R. Beyar, N. Lotan, S. S. Sivan

Research output: Contribution to journalArticle

Abstract

Coronary stenosis due to atherosclerosis, the primary cause of coronary artery disease, is generally treated by balloon dilatation and stent implantation, which can result in damage to the endothelial lining of blood vessels. This leads to the restenosis of the lumen as a consequence of migration and proliferation of smooth muscle cells (SMCs). Nitric oxide (NO), which is produced and secreted by vascular endothelial cells (ECs), is a central anti-inflammatory and anti-atherogenic player in the vasculature. The goal of the present study was to develop an enzymatically active surface capable of converting the prodrug l-arginine, to the active drug, NO, thus providing a targeted drug delivery interface. NO synthase (NOS) was chemically immobilized on the surface of a stainless steel carrier with preservation of its activity. The ability of this functionalized NO-producing surface to prevent or delay processes involved in restenosis and thrombus formation was tested. This surface was found to significantly promote EC adhesion and proliferation while inhibiting that of SMCs. Furthermore, platelet adherence to this surface was markedly inhibited. Beyond the application considered here, this approach can be implemented for the local conversion of any systemically administered prodrug to the active drug, using catalysts attached to the surface of the implant.

Original languageEnglish (US)
Pages (from-to)2304-2312
Number of pages9
JournalActa Biomaterialia
Volume10
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Drug targeting
  • Hemocompatibility
  • Immobilized enzyme
  • Nitric oxide
  • Restenosis

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Medicine(all)

Fingerprint Dive into the research topics of 'The formation of an anti-restenotic/anti-thrombotic surface by immobilization of nitric oxide synthase on a metallic carrier'. Together they form a unique fingerprint.

  • Cite this

    Alagem-Shafir, M., Kivovich, E., Tzchori, I., Lanir, N., Falah, M., Flugelman, M. Y., Dinnar, U., Beyar, R., Lotan, N., & Sivan, S. S. (2014). The formation of an anti-restenotic/anti-thrombotic surface by immobilization of nitric oxide synthase on a metallic carrier. Acta Biomaterialia, 10(5), 2304-2312. https://doi.org/10.1016/j.actbio.2013.12.043