The phosphatidylcholine/lysophosphatidylcholine ratio in human plasma is an indicator of the severity of rheumatoid arthritis: Investigations by 31P NMR and MALDI-TOF MS

Fuchs, Beate; Schiller, Jürgen; Wagner, Ulf; Häntzschel, H; Arnold, Klaus

doi:10.1016/j.clinbiochem.2005.06.006

Cited by 180 publications

(132 citation statements)

References 41 publications

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“…With respect to this, Kim et al ( 58 ) have recently described, in middle-aged men, a positive correlation between age-related changes in LPC16:0 and 8-epi-PGF 2 ␣ , a reliable marker of oxidative stress . In addition, different studies have reported an increase in plasma concentration of saturated LPC in disease conditions such as obesity, diabetes, and rheumatoid arthritis ( 59 ). Levels of LPC containing C18:0 and C16:0 saturated FAs showed an increasing trend after intervention with 3.…”

Section: Discussionmentioning

confidence: 84%

Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk

Padró

Vilahur

Sánchez-Hernández

et al. 2015

Journal of Lipid Research

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The prevalence of overweight and obesity is increasing and represents a primary health concern due to the relationship between obesity and a number of diseases and comorbidities including hyperlipidemia, a major risk factor for atherosclerosis and CVD. Dyslipidemias, typically characterized by high serum LDL cholesterol (LDLc), or low levels of HDL cholesterol (HDLc), and/or elevated triglyceride (TGL) levels, are common among patients with established CVD, type 2 diabetes mellitus, and the metabolic syndrome ( 1 ).Because cholesterol lowering is a major target for reducing CVD risk ( 2 ), dietary interventions to reduce LDLc levels in individuals with borderline dyslipidemia and obesity without overall cardiovascular risk are becoming mandatory. Cholesterol concentrations within the circulatory pool are products of input from gut absorption and endogenous synthesis relative to clearance through Abstract The benefi ts of dietary phytosterols (PhySs) and long-chain n-3 PUFA ( 3) have been linked to their effects as cholesterol-and triglyceride (TGL)-lowering agents. However, it remains unknown whether these compounds have further metabolic effects on LDL lipid composition. Here, we studied the effects of PhyS-or 3-supplemented low-fat milk (milk) on the LDL-lipidome. Overweight and moderately hypercholesterolemic subjects (n = 32) were enrolled in a two-arm longitudinal crossover study. Milk (250 ml/day), enriched with either 1.57 g PhyS or 375 mg 3 (EPA + DHA), was given to the participants during two sequential 28 day intervention periods. Compared with baseline, PhyS-milk induced a higher reduction in the LDL cholesterol (LDLc) level than 3-milk. LDL resistance to oxidation was signifi cantly increased after intervention with PhyS-milk. Changes in TGL and VLDL cholesterol were only evident after 3-milk intake. Lipidomic analysis revealed a differential effect of the PhyS-and 3-milk interventions on the LDL lipid metabolite pattern. Content in LDL-glycerophospholipids was reduced after PhySmilk intake, with major changes in phosphatidylcholine (PC) and phosphatidylserine subclasses, whereas 3-milk induced signifi cant changes in the long-chain polyunsaturated cholesteryl esters and in the ratio PC36:5/lysoPC16:0, associated to a reduced infl ammatory activity. In conclusion, daily intake of milk products containing PhyS or 3 supplements induce changes in the LDL-lipidome that indicate reduced infl ammatory and atherogenic effects, beyond their LDLc-and TGL-lowering effects. -Padro, T., G. Vilahur, J. S á nchez-Hern á ndez, M. Hern á ndez, R. M. Antonijoan, A. Perez, and L. Badimon. Lipidomic changes of LDL in overweight and moderately hypercholesterolemic

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Section: Discussionmentioning

confidence: 84%

Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk

Padró

Vilahur

Sánchez-Hernández

et al. 2015

Journal of Lipid Research

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“…Lipids play important roles in regulating and controlling cellular functions and are involved in human physical and pathological conditions (1)(2)(3)(4)(5)(6). Lipidomics, the large-scale study of pathways and networks of cellular lipids in biological systems ( 7,8 ), is an emerging fi eld of basic and translational research.…”

Section: Supplementary Abstract Hplc-esi-ms/ms • Meoh Methods • Cell mentioning

confidence: 99%

An extremely simple method for extraction of lysophospholipids and phospholipids from blood samples

Zhao

2010

Journal of Lipid Research

136

100

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This article is available online at http://www.jlr.org lysophosphatidylcholine (LPC) levels in plasma may be used as potential markers of colorectal cancer ( 22 ).Extensive "omics" studies (including proteomics, genomics, and metabolomics) have been conducted in the past few years that have generated overwhelming amounts of data. However, almost none of the identifi ed markers have been moved into clinics. One of the major problems is that very few of these markers have been confi rmed and cross-examined in multiple labs. This is at least in part due to different methodologies used, which are critical for detecting the changes that occur during perturbation of the biological systems. We have discussed these issues in a recent review paper ( 23 ). One of the most critical factors clearly affecting the quantitative analysis of lipids in blood samples is extraction. Many different lipid extraction methods have been developed in the past decades and most of them are based on the original method developed by Blight and Dyer ( 24 ). In general, two organic solvents [methanol (MeOH) and chloroform] are used, and phase separation is involved. Lipids are dissolved in these solvents, and proteins and other hydrophilic materials are removed after phase separation. The original Bligh and Dyer method (BD method) is suitable for extracting major membrane phospholipids (PLs), including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and certain membrane sphingolipids. However, it is very poor in extracting lysophospholipids (LPLs), which are more hydrophilic. Modifi cations have been made to increase the effi ciency of extracting these signaling molecules. We have improved LPA extraction by Abstract Lipids, lysophospholipids and phospholipids in particular, have been shown to be biomarkers and potential therapeutic targets for human diseases. While many extraction and analytical methods have been developed for quantitative analyses of these molecules, most of them are laborious and time-consuming, with associated issues of poor reproducibility. This becomes one of the critical bottle-necks to move lipid markers to clinics. In the current work, we have developed an extremely simple method for lysophospholipids and phospholipids extraction from human plasma or serum samples, which only utilizes a single methanol (MeOH) solvent and involves a single step of centrifugation. This method has been subjected to strict validation by comparing it with classical lipid extraction methods. This simple method will be extremely useful for the lipidomic, diseases marker, and lipid biochemistry fi elds not only for its potential wide applications associated with its simplicity and reproducibility, but also for its impact in moving lipid markers into clinics through high-throughput processing. -Zhao, Z., and Y. Xu. An extremely simple method for extraction of lysophospholipids and phospholipids from blood samples. J Lipid Res . 2010. 51: 652-659. Supplementary ...

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“…In summary, the observation that the functional responses of FLS to inflammatory stimuli resemble those induced by LPA in various cell types, that ATX mRNA is expressed by RA synoviocytes (Kehlen et al, 2001), and that RA synovial fluid contains significant amounts of the LPA precursor lysophosphatidylcholine (LPC) (Fuchs et al, 2005), led us to the investigation of the expression profile and the functional responses of LPA 1-3 receptors in FLS. We report that LPA 1 , LPA 2 , and LPA 3 receptor mRNA is expressed in FLS.…”

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confidence: 99%

Regulation of Lysophosphatidic Acid Receptor Expression and Function in Human Synoviocytes: Implications for Rheumatoid Arthritis?

Chang¹,

Fernandes²,

Prestwich

et al. 2007

Mol Pharmacol

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Lysophosphatidic acid (LPA), via interaction with its G-protein coupled receptors, is involved in various pathological conditions. Extracellular LPA is mainly produced by the enzyme autotaxin (ATX). Using fibroblast-like synoviocytes (FLS) isolated from synovial tissues of patients with rheumatoid arthritis (RA), we studied the expression profile of LPA receptors, LPAinduced cell migration, and interleukin (IL)-8 and IL-6 production. We report that FLS express LPA receptors LPA 1-3 . Moreover, exogenously applied LPA induces FLS migration and secretion of IL-8/IL-6, whereas the LPA 3 agonist L-sn-1-Ooleoyl-2-methyl-glyceryl-3-phosphothionate (2S-OMPT) stimulates cytokine synthesis but not cell motility. The LPA-induced FLS motility and cytokine production are suppressed by LPA 1/3 receptor antagonists diacylglycerol pyrophosphate and (S)-phosphoric acid mono-(2-octadec-9-enoylamino-3-[4-(pyridine-2-ylmethoxy)-phenyl]-propyl) ester (VPC32183). Signal transduction through p42/44 mitogen-activated protein kinase (MAPK), p38 MAPK, and Rho kinase is involved in LPA-mediated cytokine secretion, whereas LPA-induced cell motility requires p38 MAPK and Rho kinase but not p42/44 MAPK. Treatment of FLS with tumor necrosis factor-␣ (TNF-␣) increases LPA 3 mRNA expression and correlates with enhanced LPA-or OMPT-induced cytokine production. LPA-mediated superproduction of cytokines by TNF-␣-primed FLS is abolished by LPA 1/3 receptor antagonists. We also report the presence of ATX in synovial fluid of patients with RA. LPA 1/3 receptor antagonists and ATX inhibitors reduce the synovial fluid-induced cell motility. Together the data suggest that LPA 1 and LPA 3 may contribute to the pathogenesis of RA through the modulation of FLS migration and cytokine production. The above results provide novel insights into the relevance of LPA receptors in FLS biology and as potential therapeutic targets for the treatment of RA.

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The phosphatidylcholine/lysophosphatidylcholine ratio in human plasma is an indicator of the severity of rheumatoid arthritis: Investigations by 31P NMR and MALDI-TOF MS

Cited by 180 publications

References 41 publications

Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk

Lipidomic changes of LDL in overweight and moderately hypercholesterolemic subjects taking phytosterol- and omega-3-supplemented milk

An extremely simple method for extraction of lysophospholipids and phospholipids from blood samples

Regulation of Lysophosphatidic Acid Receptor Expression and Function in Human Synoviocytes: Implications for Rheumatoid Arthritis?

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