Interleukin-33 rescues perivascular adipose tissue anticontractile function in obesity

Saxton, SN ORCID: https://orcid.org/0000-0002-3067-1652, Whitley, AS, Potter, RJ ORCID: https://orcid.org/0000-0003-4145-647X, Withers, SB ORCID: https://orcid.org/0000-0002-7021-881X, Grencis, R and Heagerty, AM 2020, 'Interleukin-33 rescues perivascular adipose tissue anticontractile function in obesity' , American Journal of Physiology-Heart and Circulatory Physiology, 319 (6) , H1387-H1397.

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Abstract

Perivascular adipose tissue (PVAT) depots are metabolically active and play a major vasodilator role in healthy lean individuals. In obesity, they become inflamed and eosinophil-depleted and the anticontractile function is lost with the development of diabetes and hypertension. Moreover, eosinophil-deficient ΔdblGATA-1 mice lack PVAT anticontractile function and exhibit hypertension. Here, we have investigated the effects of inducing eosinophilia on PVAT function in health and obesity. Control, obese, and ΔdblGATA-1 mice were administered intraperitoneal injections of interleukin-33 (IL-33) for 5 days. Conscious restrained blood pressure was measured, and blood was collected for glucose and plasma measurements. Wire myography was used to assess the contractility of mesenteric resistance arteries. IL-33 injections induced a hypereosinophilic phenotype. Obese animals had significant elevations in blood pressure, blood glucose, and plasma insulin, which were normalized with IL-33. Blood glucose and insulin levels were also lowered in lean treated mice. In arteries from control mice, PVAT exerted an anticontractile effect on the vessels, which was enhanced with IL-33 treatment. In obese mice, loss of PVAT anticontractile function was rescued by IL-33. Exogenous application of IL-33 to isolated arteries induced a rapidly decaying endothelium-dependent vasodilation. The therapeutic effects were not seen in IL-33-treated ΔdblGATA-1 mice, thereby confirming that the eosinophil is crucial. In conclusion, IL-33 treatment restored PVAT anticontractile function in obesity and reversed development of hypertension, hyperglycemia, and hyperinsulinemia. These data suggest that targeting eosinophil numbers in PVAT offers a novel approach to the treatment of hypertension and type 2 diabetes in obesity.

Item Type: Article
Additional Information: ** From Crossref journal articles via Jisc Publications Router **Journal IDs: pissn 0363-6135; eissn 1522-1539 **History: issued 01-12-2020; published 01-12-2020
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: American Journal of Physiology-Heart and Circulatory Physiology
Publisher: American Physiological Society
ISSN: 0363-6135
Related URLs:
Funders: British Heart Foundation
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 11 Dec 2020 11:20
Last Modified: 11 Dec 2020 11:30
URI: http://usir.salford.ac.uk/id/eprint/59073

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