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

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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.

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Acknowledgements

Edmund WC Khong of Eastern Health Clinical School, Monash University, Australia: for Data interpretation; Dr David Jones of Bio21 Institute, The University of Melbourne, Australia for SonoTek spray coater; National Health and Medical Research Council of Australia Grant 1113681; National Heart Foundation of Australia, Future leader fellowship ID:102068 Australian Research Council, Grant LE100100147; Medtronic Australasia Pty and Abbott Australasia Pty Lt, PABA; and IN.PACT Admiral DEBc.

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Authors and Affiliations

  1. Eastern Health Clinical School, Monash University, Clayton, Australia

    HongBin Liu & Anthony E. Dear

  2. Baker Heart and Diabetes Institute, Melbourne, Australia

    Melissa Byrne, Yung-Chih Chen & David M. Kaye

  3. Department of Chemistry, Monash University, Melbourne, Australia

    Patrick Perlmutter, Ashley Walker & Gopal R. Sama

  4. Bio21 Institute, Melbourne University, Melbourne, Australia

    Jegadesan Subbiah

  5. CSIRO Biomedical Translational Facility, Melbourne, Australia

    Berkay Ozcelik

  6. Department of Pharmacology, Monash University, Melbourne, Australia

    Robert E. Widdop & Tracey A. Gaspari

  7. BasePair Genomics, Melbourne, Australia

    Keith Byron

Authors
  1. HongBin Liu
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  2. Melissa Byrne
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  3. Patrick Perlmutter
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  11. Yung-Chih Chen
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  13. Anthony E. Dear
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Corresponding author

Correspondence to Anthony E. Dear.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

All procedures performed in studies involving animals were in accordance with the ethical standards of the Baker Heart and Diabetes Institute Animal Ethics Committee, Melbourne, Australia, Approval number 1513767.1.

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HongBin Liu and Melissa Byrne equal first author.

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Liu, H., Byrne, M., Perlmutter, P. et al. A Novel Epigenetic Drug-Eluting Balloon Angioplasty Device: Evaluation in a Large Animal Model of Neointimal Hyperplasia. Cardiovasc Drugs Ther 33, 687–692 (2019). https://doi.org/10.1007/s10557-019-06921-w

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