TLRs and RAGE are elevated in carotid plaques from patients with moderate-to-severe obstructive sleep apnea syndrome

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.