A Novel Epigenetic Drug-Eluting Balloon Angioplasty Device: Evaluation in a Large Animal Model of Neointimal Hyperplasia

HongBin Liu, Melissa Byrne, Patrick Perlmutter, Ashley Walker, Gopal R. Sama, Jegadesan Subbiah, Berkay Ozcelik, Robert E. Widdop, Tracey A. Gaspari, Keith Byron, Yung-Chih Chen, David M. Kaye, Anthony E. Dear

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Abstract

Purpose: Drug-eluting balloon catheters (DEBc) coated with paclitaxel (PTX) have been associated with potential safety concerns. An efficacious but less toxic balloon coating may reduce these outcomes. We evaluated a novel DEBc, Epi-Solve, coated with metacept-3 (MCT-3), a member of the histone deacetylase inhibitor (HDACi) class of epigenetic agents, in a large animal model of neointimal hyperplasia (NIH). Methods: Plain balloon angioplasty (PABA) catheters were ultrasonically coated with MCT-3 to generate Epi-Solve DEBc. An ovine model of NIH formation was established utilising partial left common carotid artery (LCA) ligation. Twenty-eight days post neointima (NI) induction, PABA, Epi-Solve or PTX-coated DEBc were deployed at the site of induced NI formation. Twenty-eight days post-intervention, ligated vessels were evaluated for attenuation of NI formation, gene expression profiles and immunohistochemical analysis. Results: Epi-Solve DEBc demonstrated attenuation of NIH over no intervention and a trend to inhibition of NIH over PABA. Gene expression analysis and immunohistochemical studies identified significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA. Conclusions: Epi-Solve is a novel HDACi-coated DEBc which demonstrates significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA in an ovine model and may afford endothelial protection.

Original languageEnglish
Pages (from-to)687-692
Number of pages6
JournalCardiovascular Drugs and Therapy
Volume33
Issue number6
DOIs
Publication statusPublished - 30 Dec 2019

Keywords

  • Drug-eluting balloon angioplasty
  • Epigenetic
  • Neointimal hyperplasia

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