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Abstract
Following myocardial infarction (MI), elderly patients have a poorer prognosis than younger patients, which may be linked to increased coronary microvessel susceptibility to injury. Interleukin-36 (IL-36), a newly discovered proinflammatory member of the IL-1 superfamily, may mediate this injury, but its role in the injured heart is currently not known. We first demonstrated the presence of IL-36(α/β) and its receptor (IL-36R) in ischemia/reperfusion-injured (IR-injured) mouse hearts and, interestingly, noted that expression of both increased with aging. An intravital model for imaging the adult and aged IR-injured beating heart in real time in vivo was used to demonstrate heightened basal and injury-induced neutrophil recruitment, and poorer blood flow, in the aged coronary microcirculation when compared with adult hearts. An IL-36R antagonist (IL-36Ra) decreased neutrophil recruitment, improved blood flow, and reduced infarct size in both adult and aged mice. This may be mechanistically explained by attenuated endothelial oxidative damage and VCAM-1 expression in IL-36Ra-treated mice. Our findings of an enhanced age-related coronary microcirculatory dysfunction in reperfused hearts may explain the poorer outcomes in elderly patients following MI. Since targeting the IL-36/IL-36R pathway was vasculoprotective in aged hearts, it may potentially be a therapy for treating MI in the elderly population.
Original language | English |
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Article number | e155236 |
Number of pages | 19 |
Journal | JCI Insight |
Volume | 7 |
Issue number | 5 |
Early online date | 3 Feb 2022 |
DOIs | |
Publication status | Published - 8 Mar 2022 |
Bibliographical note
Funding Information:This work was supported by the British Heart Foundation (FS/18/45/33862).
Keywords
- Myocardial infarction
- coronary microcirculation
- ageing
- ischaemia-reperfusion injury
- neutrophils
- platelets
- interleukin-36
ASJC Scopus subject areas
- General Medicine
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Dive into the research topics of 'Targeting IL-36 improves age-related coronary microcirculatory dysfunction and attenuates myocardial ischemia/ reperfusion injury in mice: ageing and the coronary microcirculation'. Together they form a unique fingerprint.Projects
- 1 Finished
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The Role of IL-36 in Mediating Microcirculatory Disturbance in the Young and Aged Murine Heart After Myocardial Ischaemis-Reperfusion Injury
Kavanagh, D. (Co-Investigator), Kalia, N. (Principal Investigator) & Drury, N. (Co-Investigator)
4/03/19 → 3/03/22
Project: Research