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Microcirculation - 2023 - Naser - Advanced glycated end‐products inhibit dilation through constitutive endothelial RAGE and5.47 MB
Published VersionCC BY V4.0, Open Access
Journal article
Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries
Microcirculation, Vol.31(1), pp.1-14
2024
Abstract
Objective:
This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA).
Methods:
Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography.
Results:
High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619.
Conclusion:
These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.
Details
- Title
- Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries
- Authors
- Nadim Naser (Author) - UNSW SydneyChenchel K Lonj (Author) - UNSW SydneyMatthew Rikard-Bell (Author) - UNSW SydneyShaun L Sandow (Author) - University of the Sunshine Coast, Queensland, School of Health - BiomedicineTimothy V Murphy (Corresponding Author) - UNSW Sydney
- Publication details
- Microcirculation, Vol.31(1), pp.1-14
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2024
- DOI
- 10.1111/micc.12837
- ISSN
- 1549-8719; 1073-9688
- Copyright note
- © 2023 The Authors. Microcirculation published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Grant note
- National Heart Foundation of Australia
- Organisation Unit
- School of Health - Biomedicine; Healthy Ageing Research Cluster
- Language
- English
- Record Identifier
- 99980396302621
- Output Type
- Journal article
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