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

Cardiovasc Drugs Ther. 2019 Dec;33(6):687-692. doi: 10.1007/s10557-019-06921-w.

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.

Keywords: Drug-eluting balloon angioplasty; Epigenetic; Neointimal hyperplasia.

Publication types

  • Comparative Study

MeSH terms

  • Angioplasty, Balloon / instrumentation*
  • Animals
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / metabolism
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / therapy*
  • Carotid Artery, Common / metabolism
  • Carotid Artery, Common / pathology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coated Materials, Biocompatible*
  • Disease Models, Animal
  • Epigenesis, Genetic / drug effects*
  • Equipment Design
  • Female
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Neointima*
  • Paclitaxel / administration & dosage
  • Sheep, Domestic
  • Time Factors
  • Vascular Access Devices*

Substances

  • Coated Materials, Biocompatible
  • Histone Deacetylase Inhibitors
  • Inflammation Mediators
  • Paclitaxel