P735 Interleukin-33 induced eosinophilia restores perivascular adipose tissue function in obesity

Saxton, S, Potter, RJ, Withers, SB ORCID: https://orcid.org/0000-0002-7021-881X, Grencis, R and Heagerty, AM 2019, 'P735 Interleukin-33 induced eosinophilia restores perivascular adipose tissue function in obesity' , European Heart Journal, 40 (Supple) .

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Abstract

Abstract Background/Purpose Perivascular adipose tissue (PVAT) is essential in the modulation of vascular tone. Recently we have shown that resident eosinophils play a vital role in regulating PVAT function. In obesity, eosinophil numbers are reduced and PVAT anticontractile function is lost, resulting in increased vascular tone, which will contribute to development of hypertension and type-2 diabetes. Evidence suggests that eosinophilia resulting from parasitic infection may be useful in improving glucose tolerance; therefore, we investigated the effects of eosinophilia on PVAT function in health and obesity. Methods Control mice and a high fat fed mouse model of obesity were administered intraperitoneal injections of interleukin-33 (IL-33, 0.1μg) over a five day period. Blood pressure, blood glucose and plasma insulin were measured and compared with un-injected control and obese mice. Wire myography was used to assess the vascular contractility of mesenteric arteries (<250μm, +/− PVAT) from both injected and un-injected control and obese mice in response to noradrenaline. ELISAs and immunohistochemistry were used to examine eosinophil numbers. Results High fat feeding induced significant elevations in blood pressure, blood glucose and plasma insulin, which were reduced using IL-33 injections. Eosinophilia was confirmed in blood plasma using an eosinophil cationic protein ELISA. Using wire myography, mesenteric arteries from control mice PVAT exerted an anticontractile effect on the vessels, which was enhanced in control mice injected with IL-33. In obese mice, the PVAT anticontractile effect was lost, but was restored in IL-33 injected obese mice. Using immunohistochemistry, we confirm that eosinophils numbers in PVAT were reduced in obesity and increased in IL-33 treated PVAT. Conclusions IL-33 injections induced eosinophilia in both control and obese mice. IL-33 treatment restored PVAT function in obesity, and enhanced the anticontractile function of PVAT in healthy animals. In addition, only five consecutive injections of IL-33 reversed development of hypertension and type-2 diabetes in obese mice. These data suggest that IL-33 induced eosinophilia presents a novel approach to treatment of hypertension and type-2 diabetes in obesity. Acknowledgement/Funding British Heart Foundation

Item Type: Article
Additional Information: ** Article version: VoR ** From Crossref via Jisc Publications Router **Journal IDs: pissn 0195-668X; eissn 1522-9645 **History: published_online 21-10-2019; issued 01-10-2019; published 01-10-2019 **License for this article: starting on 21-10-2019, , https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
Uncontrolled Keywords: Cardiology and Cardiovascular Medicine
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: European Heart Journal
Publisher: Oxford University Press (OUP)
ISSN: 1522-9645
Related URLs:
Funders: British Heart Foundation
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 21 Jan 2020 08:34
Last Modified: 22 Jan 2020 10:06
URI: http://usir.salford.ac.uk/id/eprint/52900

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