Journal article
Plasma Exosomes Protect the Myocardium From Ischemia-Reperfusion Injury
Journal of the American College of Cardiology, Vol.65(15), pp.1525-1536
04/21/2015
DOI: 10.1016/j.jacc.2015.02.026
PMID: 25881934
Abstract
Exosomes are nanometer-sized vesicles released from cells into the blood, where they can transmit signals throughout the body. Shown to act on the heart, exosomes’ composition and the signaling pathways they activate have not been explored. We hypothesized that endogenous plasma exosomes can communicate signals to the heart and provide protection against ischemia and reperfusion injury.
This study sought to isolate and characterize exosomes from rats and healthy volunteers, evaluate their cardioprotective actions, and identify the molecular mechanisms involved.
The exosome-rich fraction was isolated from the blood of adult rats and human volunteers and was analyzed by protein marker expression, transmission electron microscopy, and nanoparticle tracking analysis. This was then used in ex vivo, in vivo, and in vitro settings of ischemia-reperfusion, with the protective signaling pathways activated on cardiomyocytes identified using Western blot analyses and chemical inhibitors.
Exosomes exhibited the expected size and expressed marker proteins CD63, CD81, and heat shock protein (HSP) 70. The exosome-rich fraction was powerfully cardioprotective in all tested models of cardiac ischemia-reperfusion injury. We identified a pro-survival signaling pathway activated in cardiomyocytes involving toll-like receptor (TLR) 4 and various kinases, leading to activation of the cardioprotective HSP27. Cardioprotection was prevented by a neutralizing antibody against a conserved HSP70 epitope expressed on the exosome surface and by blocking TLR4 in cardiomyocytes, identifying the HSP70/TLR4 communication axis as a critical component in exosome-mediated cardioprotection.
Exosomes deliver endogenous protective signals to the myocardium by a pathway involving TLR4 and classic cardioprotective HSPs.
Details
- Title: Subtitle
- Plasma Exosomes Protect the Myocardium From Ischemia-Reperfusion Injury
- Creators
- Jose M. Vicencio - The Hatter Cardiovascular Institute, University College London, London, United KingdomDerek M. Yellon - The Hatter Cardiovascular Institute, University College London, London, United KingdomVivek Sivaraman - The Hatter Cardiovascular Institute, University College London, London, United KingdomDebashish Das - The Hatter Cardiovascular Institute, University College London, London, United KingdomClaire Boi-Doku - The Hatter Cardiovascular Institute, University College London, London, United KingdomSapna Arjun - The Hatter Cardiovascular Institute, University College London, London, United KingdomYing Zheng - The Hatter Cardiovascular Institute, University College London, London, United KingdomJaime A. Riquelme - Advanced Center for Chronic DiseasesJessica Kearney - The Hatter Cardiovascular Institute, University College London, London, United KingdomVikram Sharma - University College LondonGabriele Multhoff - Klinikum rechts der IsarAndrew R. Hall - The Hatter Cardiovascular Institute, University College London, London, United KingdomSean M. Davidson - The Hatter Cardiovascular Institute, University College London, London, United Kingdom
- Resource Type
- Journal article
- Publication Details
- Journal of the American College of Cardiology, Vol.65(15), pp.1525-1536
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jacc.2015.02.026
- PMID
- 25881934
- ISSN
- 0735-1097
- eISSN
- 1558-3597
- Number of pages
- 12
- Grant note
- MR/K002066/1 / Medical Research Council RG/08/015/26411 / British Heart Foundation Department of Health’s National Institute for Health Research Biomedical Research Centres National Institute for Health Research, University College London Hospitals/University College London Biomedical Research Centre
- Language
- English
- Date published
- 04/21/2015
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984806501702771
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