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

Olejarz, Wioletta; Głuszko, Alicja; Cyran, Agata; Bednarek-Rajewska, Katarzyna; Proczka, Robert; Dl, Smith; Ishman, Stacey L.; Migacz, Ewa; Kukwa, Wojciech

doi:10.1007/s11325-020-02029-w

Cited by 12 publications

(10 citation statements)

References 35 publications

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“…In pathogenesis of atherosclerosis, a pivotal role is played by innate immunity receptors such as toll-like receptors (TLR) and receptors for advanced glycation end products (RAGE) [67]. TLR and RAGE mediate in macrophages and leukocyte recruitment and are significantly involved in the initiation and progression of atherosclerosis [68]. This process is characterized by the accumulation of lipids, smooth muscle cell proliferation, cell apoptosis, necrosis, and fibrosis [69].…”

Section: Mmps In Pathogenesis Of Atherosclerosismentioning

confidence: 99%

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Olejarz

Łacheta

Kubiak-Tomaszewska

2020

IJMS

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145

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification.

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Section: Mmps In Pathogenesis Of Atherosclerosismentioning

confidence: 99%

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Olejarz

Łacheta

Kubiak-Tomaszewska

2020

IJMS

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145

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“…Two recent studies conducted on plaques of patients with OSA support this notion. In a prospective study, Olejarz et al reported that the expression of toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE) were significantly increased in carotid plaques of moderate to severe OSA when compared with controls or with mild OSA ( 41 ). These receptors play a pivotal role in carotid plaque instability and rupture ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Markers of Carotid Plaque Destabilization in Patients With Sleep-Disordered Breathing

2022

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Sleep-disordered breathing (SDB) is a nightly respiratory condition characterized by intermittent hypoxia, leading to oxidative stress, inflammation, and atherosclerosis. However, most cellular markers of human carotid plaques in SDB have not yet been assessed. We aimed at characterizing the cellular, inflammatory, and nitro-oxidative stress markers in carotid plaques obtained from 25 patients undergoing endarterectomy and screened for SDB. Sleep studies were performed during their preoperative hospitalization night using the Watch-PAT 100 device. Oxygen desaturation index (ODI) was used for dividing patients into two groups. Fourteen patients with ODI >5 were designated as SDB and 11 patients with ODI ≤ 5 as non-SDB. Demographics, comorbidities, cardiovascular risk factors, and medications were recorded. Cellular markers in plaques were analyzed by immunofluorescence using confocal microscopy. The expression of neutrophils was identified by CD66b+ and neutrophil elastase, macrophage-foam cells were identified by CD163+, and scavenger receptors by CD68+ and CD36+ expression. Additional markers included 3-nitrotyrosine, endothelial CD31, and smooth muscle cell-actin (SMC-actin). Plaques' lipids were determined by immunohistochemistry with Oil Red O staining. Notably, significantly higher values were found for SDB as compared to patients with non-SDB for 3-nitrotyrosine (p <0.004) and intracellular lipids' content (p <0.02), whereas SMC-actin was lower (p <0.006). There were no significant differences between patients with carotid-associated symptoms (symptomatic) and patients without carotid-associated symptoms (asymptomatic). However, a sub-group of symptomatic patients with co-existent SDB expressed the highest 3-nitrotyrosin, and intracellular lipids levels, and the lowest SMC-actin levels, whereas non-SDB/asymptomatic patients expressed the lowest 3-nitrotyrosin and lipids levels and the highest SMS-actin levels among all patients. Accordingly, ODI was lowest in non-SDB/asymptomatic patients and highest in SDB/symptomatic. In conclusion, plaques of patients with SDB were characterized by markedly increased levels of 3-nitrotyrosine and intracellular lipids content. Conversely, SMC-actin levels were significantly lower. These three markers, such as increased 3-nitrotyrosine and intracellular lipids and decreased SMC-actin are associated with plaque vulnerability and instability. These findings are in line with earlier reports demonstrating increased intima-media thickness in large cohorts of sleep apnea and patients with SDB, and thus, may indicate a higher susceptibility to plaque vulnerability and rapture in patients with SDB.

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“…That confirms cysteinyl-leukotrienes (CysLT) pathway activation as a potential mechanism responsible for developing atherosclerosis connected with IH [ 22 ]. Another study trying to explain OSA-dependent atherogenesis found an increased expression of toll-like receptors (TLRs) and receptor for advanced glycation end-products (RAGE) in atherosclerotic plaques from patients with severe OSA [ 23 ].…”

Section: Molecular Consequences Of Hypoxia/reoxygenation (H/r) On Endothelial Function In Osa Before Cpap Treatmentmentioning

confidence: 99%

“…(TLRs) and receptor for advanced glycation end-products (RAGE) in atherosclerotic plaques from patients with severe OSA [23].…”

Section: Molecular Consequences Of Hypoxia/reoxygenation (H/r) On Endothelial Function In Osa Before Cpap Treatmentmentioning

confidence: 99%

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

Mochol

Gawryś

Gajecki

et al. 2021

IJMS

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Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke.

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

Cited by 12 publications

References 35 publications

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Markers of Carotid Plaque Destabilization in Patients With Sleep-Disordered Breathing

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

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