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Effects of Colchicine on Atherosclerotic Plaque Stabilization: a Multimodality Imaging Study in an Animal Model

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Abstract

Colchicine demonstrated clinical benefits in the treatment of stable coronary artery disease. Our aim was to evaluate the effects of colchicine on atherosclerotic plaque stabilization. Atherosclerosis was induced in the abdominal aorta of 20 rabbits with high-cholesterol diet and balloon endothelial denudation. Rabbits were randomized to receive either colchicine or placebo. All animals underwent MRI, 18F-FDG PET/CT, optical coherence tomography (OCT), and histology. Similar progression of atherosclerotic burden was observed in the two groups as relative increase of normalized wall index (NWI). Maximum 18F-FDG standardized uptake value (meanSUVmax) decreased after colchicine treatment, while it increased in the placebo group with a trend toward significance. Animals with higher levels of cholesterol showed significant differences in favor to colchicine group, both as NWI at the end of the protocol and as relative increase in meanSUVmax. Colchicine may stabilize atherosclerotic plaque by reducing inflammatory activity and plaque burden, without altering macrophage infiltration or plaque typology.

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Abbreviations

18F-FDG PET/CT:

18F-Fluorodeoxyglucose integrated with computed tomography

MRI:

Magnetic resonance imaging

NWI:

Normalized wall index

OCT:

Optical coherence tomography

SUV:

Standardized uptake values

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Funding

This work was supported by a grant from the Sociedad Española de Cardiología, a grant from the Instituto de Salud Carlos III of Spain and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (FIS-FEDER PI14-01427 to J. Mateo) and a grant from Fundación BBVA to J. Ruiz-Cabello. The CNIC is supported by the Instituto de Salud Carlos III, the Ministry of Science and Innovation and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). CIC biomaGUNE is supported by the Spanish State Research Agency of MICIN under the María de Maeztu Units of Excellence Program from MDM-2017-0720.

Author information

Author notes

  1. Alberto Cecconi and Jean Paul Vilchez-Tschischke contributed equally to this work.

Authors and Affiliations

  1. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Calle de Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    Alberto Cecconi, Jean Paul Vilchez-Tschischke, Jesus Mateo, Samuel España, Rodrigo Fernandez-Jimenez, Beatriz Lopez-Melgar, Leticia Fernández Friera, Gonzalo J López-Martín, Valentin Fuster & Borja Ibañez

  2. Servicio de Cardiología, Hospital Universitario de La Princesa, Madrid, Spain

    Alberto Cecconi

  3. Servicio de Cardiología, Complejo hospitalario Ruber Juan Bravo, Madrid, Spain

    Jean Paul Vilchez-Tschischke

  4. Philips Healthcare, Madrid, Spain

    Javier Sanchez-Gonzalez

  5. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA

    Rodrigo Fernandez-Jimenez & Valentin Fuster

  6. CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

    Rodrigo Fernandez-Jimenez, Beatriz Lopez-Melgar, Leticia Fernández Friera & Borja Ibañez

  7. Servicio de Cardiología, Hospital Universitario HM Puerta del Sur, Móstoles, Spain

    Beatriz Lopez-Melgar

  8. HM Hospitales - Centro Integral de Enfermedades Cardiovasculares HM-CIEC, Madrid, Spain

    Leticia Fernández Friera

  9. CIC biomaGUNE, 20014, Donostia-San Sebastián, Spain

    Jesus Ruiz-Cabello

  10. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

    Jesus Ruiz-Cabello

  11. CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain

    Jesus Ruiz-Cabello

  12. Universidad Complutense Madrid, Madrid, Spain

    Jesus Ruiz-Cabello

  13. Servicio de Cardiología, IIS - Fundación Jiménez Díaz Hospital, Madrid, Spain

    Borja Ibañez

Authors
  1. Alberto Cecconi
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  2. Jean Paul Vilchez-Tschischke
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  3. Jesus Mateo
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  4. Javier Sanchez-Gonzalez
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  5. Samuel España
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  6. Rodrigo Fernandez-Jimenez
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  7. Beatriz Lopez-Melgar
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  8. Leticia Fernández Friera
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  9. Gonzalo J López-Martín
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  10. Valentin Fuster
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  11. Jesus Ruiz-Cabello
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  12. Borja Ibañez
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Corresponding author

Correspondence to Borja Ibañez.

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This article does not contain any studies with human participants performed by any of the authors. All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees.

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Associate Editor Paul J. R. Barton oversaw the review of this article

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Cecconi, A., Vilchez-Tschischke, J.P., Mateo, J. et al. Effects of Colchicine on Atherosclerotic Plaque Stabilization: a Multimodality Imaging Study in an Animal Model. J. of Cardiovasc. Trans. Res. 14, 150–160 (2021). https://doi.org/10.1007/s12265-020-09974-7

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  • DOI: https://doi.org/10.1007/s12265-020-09974-7

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