Capillary pericytes mediate coronary no-reflow after myocardial ischaemia
- University College London, United Kingdom
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
Fergus M O'Farrell
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.
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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Capillary pericytes mediate coronary no-reflow after myocardial ischaemia
eLife 6:e29280.
https://doi.org/10.7554/eLife.29280
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