TLRs and RAGE are elevated in carotid plaques from patients with moderate-to-severe obstructive sleep apnea syndrome
Open Access
- 20 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Sleep and Breathing
- Vol. 24 (4), 1573-1580
- https://doi.org/10.1007/s11325-020-02029-w
Abstract
Background There is growing evidence that obstructive sleep apnea (OSA) promotes vascular endothelial dysfunction and atherogenesis. Pathways that mediate this pathology may include Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) which play a significant role in proinflammatory processes. The aim of this study was to measure the expression of the above-mentioned receptors in relation to OSA severity in carotid plaques obtained during open endarterectomy. Methods This prospective study included patients with a sleep study prior to surgery and a plaque specimen obtained during standard open endarterectomy. Immunohistochemistry of TLR2, TLR4, TLR7, TLR9, RAGE, HMGB1, and NF-κB was performed on atherosclerotic plaques from carotid arteries of patients with and without OSA. Results There were 46 patients (22 women, mean age 73.2 ± 1.3 years): 14 control patients, 13 with mild, 11 with moderate, and 8 with severe OSA. The expression of all TLRs and RAGE increased proportionately with increasing OSA severity. The largest differences between patients with severe OSA and no OSA were found for TLR2 (2.88 ± 0.35 vs. 1.27 ± 0.47, p < 0.001), TLR4 (2.88 ± 0.35 vs. 1.64 ± 0.5, p < 0.001), TLR9 (2.38 ± 0.52 vs. 1.45 ± 0.52, p < 0.01), and RAGE (2.5 ± 0.53 vs. 1.82 ± 0.6, p < 0.05). Conclusion TLR2, TLR4, TLR9, and RAGE expression was significantly increased in carotid plaques of patients with moderate-to-severe OSA when compared with control patients with no OSA and those with mild OSA. TLR and RAGE-mediated pathways may play a significant role in OSA-dependent atherogenesis.Keywords
Funding Information
- Narodowym Centrum Nauki (2017/01/X/NZ3/00248)
This publication has 34 references indexed in Scilit:
- Patients with Obstructive Sleep Apnea Display Increased Carotid Intima Media: A Meta-AnalysisInternational Journal of Vascular Medicine, 2013
- Simvastatin suppresses vascular inflammation and atherosclerosis in ApoE−/− mice by downregulating the HMGB1-RAGE axisActa Pharmacologica Sinica, 2013
- Dissecting negative regulation of Toll-like receptor signalingTrends in Immunology, 2012
- Role of Toll-Like Receptor 4 in Intimal Foam Cell Accumulation in Apolipoprotein E–Deficient MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2011
- Atherogenic Lipids and Lipoproteins Trigger CD36-TLR2-Dependent Apoptosis in Macrophages Undergoing Endoplasmic Reticulum StressCell Metabolism, 2010
- Obstructive Sleep Apnoea: From pathogenesis to treatment: Current controversies and future directionsRespirology, 2010
- Hyperglycemia-Induced Reactive Oxygen Species Increase Expression of the Receptor for Advanced Glycation End Products (RAGE) and RAGE LigandsDiabetes, 2009
- Emerging role of Toll-like receptors in atherosclerosisJournal of Lipid Research, 2009
- Receptor for Advanced Glycation End Products (RAGE) Deficiency Attenuates the Development of Atherosclerosis in DiabetesDiabetes, 2008
- Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic eventsThe Journal of Experimental Medicine, 2008