Resistin mediates sex-dependent effects of perivascular adipose tissue on vascular function in the SHRSP

Small, H. Y., McNeilly, S., Mary, S., Sheikh, A. M. and Delles, C. (2019) Resistin mediates sex-dependent effects of perivascular adipose tissue on vascular function in the SHRSP. Scientific Reports, 9, 6897. (doi:10.1038/s41598-019-43326-z) (PMID:31053755) (PMCID:PMC6499830)

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Abstract

Premenopausal women are relatively protected from developing hypertension compared to men. Perivascular adipose tissue (PVAT) has been shown to mediate vasoactive effects; however, a sex-dependent difference in PVAT function in the setting of hypertension has not yet been explored. We investigated the effect of PVAT on resistance vessel biology in male and female 16 week old stroke prone spontaneously hypertensive rats (SHRSP). This preclinical model of hypertension exhibits a sex-dependent difference in the development of hypertension similar to humans. Wire myography was used to assess vascular function in third-order mesenteric arteries. KATP channel-mediated vasorelaxation by cromakalim was significantly impaired in vessels from SHRSP males + PVAT relative to females (maximum relaxation: male + PVAT 46.9 ± 3.9% vs. female + PVAT 97.3 ± 2.7%). A cross-over study assessing the function of male PVAT on female vessels confirmed the reduced vasorelaxation response to cromakalim associated with male PVAT (maximum relaxation: female + PVATfemale 90.6 ± 1.4% vs. female + PVATmale 65.8 ± 3.5%). In order to explore the sex-dependent differences in PVAT at a molecular level, an adipokine array and subsequent western blot validation identified resistin expression to be increased approximately 2-fold in PVAT from male SHRSP vessels. Further wire myography experiments showed that pre-incubation with resistin (40 ng/ml) significantly impaired the ability of female + PVAT vessels to relax in response to cromakalim (maximum relaxation: female + PVAT 97.3 ± 0.9% vs. female + PVAT + resistin[40ng/ml] 36.8 ± 2.3%). These findings indicate a novel role for resistin in mediating sex-dependent vascular function in hypertension through a KATP channel-mediated mechanism.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Small, Miss Heather and Sheikh, Mr Adam and MCNEILLY, Sarah and Delles, Professor Christian
Authors: Small, H. Y., McNeilly, S., Mary, S., Sheikh, A. M., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Scientific Reports 9: 6897
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
492454BHF 4 Year PhD ProgrammeAnna DominiczakBritish Heart Foundation (BHF)FS/12/66/30003RI CARDIOVASCULAR & MEDICAL SCIENCES
593511SysVascChristian DellesEuropean Commission (EC)603288RI CARDIOVASCULAR & MEDICAL SCIENCES
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES