Bibliographic Details
| Title: |
Targeting IL-36 improves age-related coronary microcirculatory dysfunction and attenuates myocardial ischemia/reperfusion injury in mice |
| Authors: |
Juma El-Awaisi, Dean P.J. Kavanagh, Marco R. Rink, Chris J. Weston, Nigel E. Drury, Neena Kalia |
| Source: |
JCI Insight, Vol 7, Iss 5 (2022) |
| Publisher Information: |
American Society for Clinical investigation, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
Aging, Inflammation, Medicine |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2379-3708 |
| Relation: |
https://doaj.org/toc/2379-3708 |
| DOI: |
10.1172/jci.insight.155236 |
| Access URL: |
https://doaj.org/article/ce0d8a51a5314581bed63a00d79bb977 |
| Accession Number: |
edsdoj.0d8a51a5314581bed63a00d79bb977 |
| Database: |
Directory of Open Access Journals |
