Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain <scp>bEND</scp>.3 endothelial cells

Tsai, Tien Yao; Leong, Iat Lon; Cheng, Ka Shun; Shiao, Lian Ru; Wong, Kar‐Lok; Chan, Paul; Leung, Yuk‐Man

doi:10.1111/fcp.12399

Cited by 11 publications

(9 citation statements)

References 27 publications

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“…You are encouraged to use the Version of Record that, when published, will replace this version. The most up-to-date-version is available at https://doi.org/10.1042/CS20210468 LPC-induced ROS generation seems to be endothelial cell typedependent since Tsai et al failed to observe this effect in cerebral bEND.3 endothelial cells [36]. Here, we found that LPC (10 -5 M) induces ROS production in a time-dependent manner in aortic endothelial cells (HAEC).…”

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 59%

“…Moreover, EGTA, an extracellular Ca +2 chelator, and Bapta-AM, an intracellular Ca +2 chelator, abrogated ROS generation induced by LPC stimulation at 15 min (figure 5C). LPC is an abundant component of oxidized low-density lipoprotein (oxLDL) [33][34][35][36], and blood LPC concentration is increased in unhealthy subjects [6,18,19], with values around 200 μmol Pi/L (micromoles of inorganic phosphate (Pi) per liter of plasma) in diabetic patients [18]. LPC activates apoptotic signaling [35][36][37], induces vascular dysfunction [33], promotes inflammatory cell infiltration of vascular walls [38], and induces innate immune trans-differentiation of endothelial cells [12].…”

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 99%

“…LPC is an abundant component of oxidized low-density lipoprotein (oxLDL) [33][34][35][36], and blood LPC concentration is increased in unhealthy subjects [6,18,19], with values around 200 μmol Pi/L (micromoles of inorganic phosphate (Pi) per liter of plasma) in diabetic patients [18]. LPC activates apoptotic signaling [35][36][37], induces vascular dysfunction [33], promotes inflammatory cell infiltration of vascular walls [38], and induces innate immune trans-differentiation of endothelial cells [12]. Upregulated ROS production contributes to the activation of signaling pathways that result in endothelial injury.…”

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 99%

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Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

et al. 2021

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Objective: The mechanisms involved in NOX5 activation in atherosclerotic processes are not completely understood. This study tested the hypothesis that lysophosphatidylcholine (LPC), a proatherogenic component of oxLDL, induces endothelial calcium influx, which drives NOX5-dependent reactive oxygen species (ROS) production, oxidative stress, and endothelial cell dysfunction. Approach: Human aortic endothelial cells (HAEC) were stimulated with LPC (10-5 M, for different time points). Pharmacological inhibition of NOX5 (Melittin, 10-7 M) and NOX5 gene silencing (siRNA) were used to determine the role of NOX5-dependent ROS production in endothelial oxidative stress induced by LPC. ROS production was determined by lucigenin assay and electron paramagnetic spectroscopy (EPR), calcium transients by Fluo4 fluorimetry, and NOX5 activity and protein expression by pharmacological assays and immunoblotting, respectively. Results: LPC increased ROS generation in endothelial cells at short (15 min) and long (4 h) stimulation times. LPC-induced ROS was abolished by a selective NOX5 inhibitor and by NOX5 siRNA. NOX1/4 dual inhibition and selective NOX1 inhibition only decreased ROS generation at 4 h. LPC increased HAEC intracellular calcium, important for NOX5 activation, and this was blocked by nifedipine and thapsigargin. Bapta-AM, selective Ca2+ chelator, prevented LPC-induced ROS production. NOX5 knockdown decreased LPC-induced ICAM-1 mRNA expression and monocyte adhesion to endothelial cells. Conclusion: These results suggest that NOX5, by mechanisms linked to increased intracellular calcium, is key to early LPC-induced endothelial oxidative stress and pro-inflammatory processes. Since these are essential events in the formation and progression of atherosclerotic lesions, this study highlights an important role for NOX5 in atherosclerosis.

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Section: Lpc Stimulates Calcium Influxmentioning

confidence: 59%

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 99%

Section: Lpc Stimulates Calcium Influxmentioning

confidence: 99%

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Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

et al. 2021

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“…In eukaryotic cells, PC is produced from phosphatidylethanolamine (PE) ( 45 ), in which LPC is an intermediate product of PC. LPC can react with acylCoA transferase in liver microparticles to produce PC ( 46 ). Besides, PC/LPC ratio in serum reflects inflammatory or infectious diseases of the liver.…”

Section: Resultsmentioning

confidence: 99%

How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics

Zhao

et al. 2021

Front. Endocrinol.

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BackgroundPolycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. And metabolic syndrome (MS) is an important bridge for PCOS patients to develop other diseases, such as diabetes and coronary heart disease. Our aim was to study the potential metabolic characteristics of PCOS-MS and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis, and treatment.MethodsIn this study, 44 PCOS patients with MS, 34 PCOS patients without MS, and 32 healthy controls were studied. Plasma samples of subjects were tested by ultraperformance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators.ResultsThere were significant differences in general characteristics, reproductive hormone, and metabolic parameters in the PCOS-MS group when compared with the PCOS group and healthy controls. We found 40 differential metabolites which were involved in 23 pathways when compared with the PCOS group. The metabolic network further reflected the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions, and metabolites. In the correlation analysis, there were 11 differential metabolites whose correlation coefficient with clinical parameters was greater than 0.4, which were expected to be taken as biomarkers for clinical diagnosis. Besides, these 11 differential metabolites were assessed by ROC, and the areas under curve (AUCs) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid + leucine + phenylalanine and carnitine C 4: 0 + carnitine C18:1 + carnitine C5:0 were expected to be sensitive combinational biomarkers in clinical practice.ConclusionOur study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.

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“…LPC is an intermediate product of PC, which is hydrolyzed by PC under the action of PLA2 or Lecithin-cholesterol acyltransferase (LCAT). LPC can react with acylCoA transferase in liver microparticles to produce PC [47].…”

Section: Differential Metabolites Between Pcos-ms Group and Hc Groupmentioning

confidence: 99%

How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics

Zhao

et al. 2021

Preprint

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Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder，with an increased risk of type 2 diabetes mellitus and cardiovascular disease, of which metabolic syndrome (MS) is an indispensable springboard to communicate PCOS and various comlications. Our aim was to study the potential metabolic characteristics of PCOS-MS, and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis and treatment.Methods: 44 PCOS patients with MS, 34 PCOS patients without MS and 32 healthy controls were studied. Plasma samples of subjects were tested by ultra performance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators.Results: There were significant difference in general characteristics, reproductive hormone and metabolic parameters in PCOS-MS group when compared with PCOS group and healthy controls. We found 30 differential metabolites which were involved in 23 pathways when compared with PCOS group. The metabolic network further reflects the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions and metabolites.In the correlation analysis, 17 pairs of correlation coefficient between differential metabolites and clincal parameters were greater than 0.4, involving 11 metabolites that has the potential to be a marker for clinical diagnosis. They were assessed by ROC whose area under curve (AUC) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid+leucine+phenylalanine and carnitine C 4: 0+carnitine C18:1+carnitine C5:0 are expected to be sensitive combinational biomarkers in clinical practice.Conclusion: Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.

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Lysophosphatidylcholine‐induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

Cited by 11 publications

References 27 publications

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

Lysophosphatidylcholine induces oxidative stress in human endothelial cells via NOX5 activation – implications in atherosclerosis

How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics

How to Screen and Prevent Metabolic Syndrome in Patients of PCOS Early: Implications From Metabolomics

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