Capillary pericytes mediate coronary no-reflow after myocardial ischaemia

Abstract

After cardiac ischaemia, a prolonged decrease of coronary microvascular perfusion often occurs even after flow is restored in an upstream artery. This 'no-reflow' phenomenon worsens patient prognosis. In the brain, after stroke, a similar post-ischaemic 'no-reflow' has been attributed to capillary constriction by contractile pericytes. We now show that occlusion of a rat coronary artery, followed by reperfusion, blocks 40% of cardiac capillaries and halves perfused blood volume within the affected region. Capillary blockages colocalised strongly with pericytes, where capillary diameter was reduced by 37%. The pericyte relaxant adenosine increased capillary diameter by 21% at pericyte somata, decreased capillary block by 25% and increased perfusion volume by 57%. Thus, cardiac pericytes constrict coronary capillaries and reduce microvascular blood flow after ischaemia, despite re-opening of the culprit artery. Cardiac pericytes are therefore a novel therapeutic target in ischaemic heart disease.

Article and author information

Author details

  1. Fergus M O'Farrell

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7378-9175
  2. Svetlana Mastitskaya

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew Hammond-Haley

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Felipe Freitas

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Wen Rui Wah

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. David Attwell

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    For correspondence
    d.attwell@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3618-0843

Funding

H2020 European Research Council (BrainPower)

  • David Attwell

Rosetrees Trust (A1188)

  • Fergus M O'Farrell
  • David Attwell

H2020 Marie Skłodowska-Curie Actions (654691)

  • Svetlana Mastitskaya

Fondation Leducq (08CVD02)

  • David Attwell

Wellcome (75232)

  • David Attwell

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were performed in accordance with European Commission Directive 2010/63/EU (European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes) and the UK government Animals (Scientific Procedures) Act (1986), with project approval from the UCL Animal Welfare and Ethical Review Body.

Reviewing Editor

  1. Fiona M Watt, King's College London, United Kingdom

Publication history

  1. Received: June 7, 2017
  2. Accepted: November 8, 2017
  3. Accepted Manuscript published: November 9, 2017 (version 1)
  4. Version of Record published: November 28, 2017 (version 2)

Copyright

© 2017, O'Farrell et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Fergus M O'Farrell
  2. Svetlana Mastitskaya
  3. Matthew Hammond-Haley
  4. Felipe Freitas
  5. Wen Rui Wah
  6. David Attwell
(2017)
Capillary pericytes mediate coronary no-reflow after myocardial ischaemia
eLife 6:e29280.
https://doi.org/10.7554/eLife.29280
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