Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein‐Associated Phospholipase A2 Plasma Activity Levels

Kheirandish‐Gozal, Leila; Philby, Mona F.; Qiao, Zhuanhong; Gozal, David

doi:10.1161/jaha.116.004923

Cited by 30 publications

(17 citation statements)

References 62 publications

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“…PLA2 is required for the remodeling and repair of cell membranes. The activation of PLA2 in children with OSA was connected to endothelial dysfunction [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

et al. 2020

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Background: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. Methods: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and five months after surgery. Results: The mean Apnea-Hypopnea Index (AHI) significantly dropped from 22.0 ± 18.5 events/hour to 8.97 ± 9.57 events/hour (p-Value < 0.001). Epworth’s sleepiness Score (ESS) dropped from 12.8 ± 6.23 to 2.95 ± 2.40 (p-Value < 0.001), indicating the success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value < 0.05), whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value < 0.05) after surgery. Conclusion: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in an improvement of the metabolic status that was characterized by decreased TG, PCs, and Cer metabolites after surgery, indicating that the success of the surgery positively impacted the metabolic status of these patients.

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“…PLA2 is required for the remodeling and repair of cell membranes. The activation of PLA2 in children with OSA was connected to endothelial dysfunction [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

et al. 2020

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“…Although high cytosolic calcium concentrations may disrupt various intracellular functions, the activation of phospholipase A1 (PLA1), A2 (PLA2) and C (PLC) is considered most damaging under hypoxic conditions 32 , 33 . A study developed in Chicago 34 was able to correlate PLA2 activation in paediatric OSA and obesity with the presence of endothelial dysfunction. Supporting causality, OSA treatment promoted PLA2 inhibition 35 .…”

Section: Discussionmentioning

confidence: 99%

Metabolomic and lipidomic profile in men with obstructive sleep apnoea: implications for diagnosis and biomarkers of cardiovascular risk

Lebkuchen

Carvalho

Venturini

et al. 2018

Sci Rep

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The use of metabolomic and lipidomic strategies for selecting potential biomarkers for obstructive sleep apnoea (OSA) has been little explored. We examined adult male patients with OSA (defined by an apnoea-hypopnoea index ≥15 events/hour), as well as age-, gender-, and fat-composition-matched volunteers without OSA. All subjects were subjected to clinical evaluation, sleep questionnaires for detecting the risk of OSA (Berlin and NoSAS score), metabolomic analysis by gas chromatography coupled to mass spectrometry and lipidomic analysis with liquid chromatography followed by detection by MALDI-MS. This study included 37 patients with OSA and 16 controls. From the 6 metabolites and 22 lipids initially selected, those with the best association with OSA were glutamic acid, deoxy sugar and arachidonic acid (metabolites), and glycerophosphoethanolamines, sphingomyelin and lyso-phosphocholines (lipids). For the questionnaires, the NoSAS score performed best with screening for OSA (area under the curve [AUC] = 0.724, p = 0.003). The combination of the NoSAS score with metabolites or lipids resulted in an AUC for detecting OSA of 0.911 and 0.951, respectively. In conclusion, metabolomic and lipidomic strategies suggested potential early biomarkers in OSA that could also be helpful in screening for this sleep disorder beyond traditional questionnaires.

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“…The increased Lp‐PLA2 level in both obstructive sleep apnea (OSA) and obesity might adversely affect endothelial integrity, which decreased after OSA treatment. Thus, plasma Lp‐PLA2 activity levels may provide a reliable biomarker for children at risk for underlying atherosclerosis and vascular dysfunction atherosclerosis in the presence of obesity or OSA . Similarly, plasma Lp‐PLA2 activity is predominantly upregulated in patients with antiphospholipid antibodies, suggesting a prognostic biomarker role for Lp‐PLA2 in managing the antiphospholipid syndrome .…”

Section: Biological Functions and Disease Implicationsmentioning

confidence: 99%

“…Thus, plasma Lp-PLA2 activity levels may provide a reliable biomarker for children at risk for underlying atherosclerosis and vascular dysfunction atherosclerosis in the presence of obesity or OSA. 230 Similarly, plasma Lp-PLA2 activity is predominantly upregulated in patients with antiphospholipid antibodies, suggesting a prognostic biomarker role for Lp-PLA2 in managing the antiphospholipid syndrome. 231 In a cohort of rheumatoid arthritis (RA) patients, the baseline Lp-PLA2 mass was significantly associated with both disease severity and subclinical atherosclerosis including IMT and flowmediated dilation at both baseline and follow-up.…”

mentioning

confidence: 99%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

Medicinal Research Reviews

122

140

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Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.

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Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein‐Associated Phospholipase A2 Plasma Activity Levels

Cited by 30 publications

References 62 publications

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

Metabolomic and lipidomic profile in men with obstructive sleep apnoea: implications for diagnosis and biomarkers of cardiovascular risk

Lipoprotein‐associated phospholipase A2: The story continues

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