Metabolism and atherogenic disease association of lysophosphatidylcholine

Schmitz, Gerd; Ruebsaamen, Katharina

doi:10.1016/j.atherosclerosis.2009.05.029

Cited by 301 publications

(236 citation statements)

References 135 publications

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“…Elevated levels of LPC and LPC(O), the precursor to platelet activating factor, in men relative to women ( Table 4 , supplementary Table II), suggests an increase in phospholipase activity (specifi cally lipoprotein-associated phospholipase A2 (Lp-PLA 2 ), also known as platelet activating factor acetylhydrolase). This enzyme is highly expressed in atherosclerotic plaque and associated with pathogenesis of atherosclerosis ( 40,41 ). This is further supported by several reports that Lp-PLA 2 activity is higher in men than women and is linked to a higher risk of CAD, reviewed by Gregson et al ( 42 ).…”

Section: Associations Of Lipids With Anthropometric and Physiologicalsupporting

confidence: 64%

Plasma lipid profiling in a large population-based cohort

Weir

Wong

Barlow

et al. 2013

Journal of Lipid Research

328

292

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This article is available online at http://www.jlr.org Circulating lipids, their biosynthesis, metabolism, and biological functions are intimately involved in many complex disease processes ( 1 ). Traditional clinical chemistry uses measurements of total cholesterol, triglycerides, and HDL as tools for determining health status and disease risk. The tests for these lipids are low cost, high throughput, and well established. The development of soft ionization techniques, particularly electrospray ionization has proven to be a watershed for lipidomics, allowing the detection and quantifi cation of individual molecular species. Recently, the Lipid Maps Consortium described a detailed analysis of the plasma lipidome, reporting on the concentration of nearly 600 lipids in pooled human plasma from healthy individuals ( 1, 2 ). This analysis highlighted the complexity of the plasma lipidome and the potential of plasma lipid profi ling for disease classifi cation, risk assessment, and to uncover changes in lipid metabolism associated with disease states. To date, plasma lipid profi ling has been used to identify lipidomic biomarkers associated with a variety of diseases and activities related to obesity ( 3 ), hypertension ( 4 ), smoking ( 5 ), cystic fi brosis ( 6 ), weight loss ( 7 ), and type 2 diabetes ( 8 ). These studies have, in general, have been conducted using relatively small cohorts (<100 participants) ( 3, 4, 6, 7 ) and/or limited coverage of the lipidome (<100 species) ( 4, 6, 8 ).Abstract We have performed plasma lipid profi ling using liquid chromatography electrospray ionization tandem mass spectrometry on a population cohort of more than 1,000 individuals. From 10 l of plasma we were able to acquire comparative measures of 312 lipids across 23 lipid classes and subclasses including sphingolipids, phospholipids, glycerolipids, and cholesterol esters (CEs) in 20 min. Using linear and logistic regression, we identifi ed statistically signifi cant associations of lipid classes, subclasses, and individual lipid species with anthropometric and physiological measures. In addition to the expected associations of CEs and triacylglycerol with age, sex, and body mass index (BMI), ceramide was signifi cantly higher in males and was independently associated with age and BMI. Associations were also observed for sphingomyelin with age but this lipid subclass was lower in males. Lysophospholipids were associated with age and higher in males, but showed a strong negative association with BMI. Many of these lipids have previously been associated with chronic diseases including cardiovascular disease and may mediate the interactions of age, sex, and obesity with disease risk. -Weir, J. M., G.

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Section: Associations Of Lipids With Anthropometric and Physiologicalsupporting

confidence: 64%

Plasma lipid profiling in a large population-based cohort

Weir

Wong

Barlow

et al. 2013

Journal of Lipid Research

328

292

View full text Add to dashboard Cite

show abstract

“…The altered individual lipid species mainly belonged to the LPC, PC, PC-O, TAG, SM, and PE lipid classes. The role of these lipid classes in the pathogenesis and progression of diabetes and atherosclerosis has recently been recognized (28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Moreover, PC (O-34:1), SM (d18:0-24:1), and SM (d18:1-20:1) were associated with an increased risk of long-term composite cardiovascular events in our study.…”

Section: Discussionsupporting

confidence: 53%

Lipid Profiling Reveals Different Therapeutic Effects of Metformin and Glipizide in Patients With Type 2 Diabetes and Coronary Artery Disease

Zhang

Hong

et al. 2014

Diabetes Care

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We recently demonstrated a beneficial effect of metformin compared with glipizide in type 2 diabetic patients regarding cardiovascular outcomes for 3-year treatment in the SPREAD-DIMCAD study. However, the potential mechanism for the clinical effects remains unclear. Here, we performed a comprehensive lipidomics study to evaluate the different lipid metabolites in serum samples obtained from participants in this study. RESEARCH DESIGN AND METHODSLiquid chromatography-quadrupole time of flight-mass spectrometry was used to evaluate the different lipid metabolites in serum samples obtained from the participants (21 patients in glipizide group and 23 patients in metformin group) before and after each year of treatment (at 0 [baseline], 1, 2, and 3 years of study drug administration). RESULTSA total of 118 serum lipid molecular species was identified and quantified. During treatment, metformin induced a substantially greater change in serum lipid species compared with glipizide, especially at the 2-and 3-year time points (with 2, 11, and 12 lipid species being significantly different between the groups after each year of treatment [1, 2, or 3 years], P < 0.05). Among the significantly changed lipid species, three lipid metabolites were linked to long-term composite cardiovascular events (adjusted P < 0.05). After treatment, triacylglycerols (TAGs) of a relatively higher carbon number showed a clearly increased trend in metformin group compared with the glipizide group, whereas the changes in TAGs with different double bonds were minimal. CONCLUSIONSOur findings revealed the differential therapeutic effects of metformin and glipizide on comprehensive lipidomics, which were comparable with their different long-term effects on cardiovascular outcomes.

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“…Statins, on the other hydrolysed by Lp-PLA2 to generate pro-inflammatory lysophosphatidylcholines (lysoPCs) (101) and recent studies have revealed very strong association between the levels of lysoPC and proinflammatory cytokines in human atherosclerotic plaques (102). Plasma levels of Lp-PLA2 and its activity have also been shown to be independent predictors of cardiovascular risk in several epidemiological studies (103).…”

Section: Anti-inflammatory Drugs and Atherosclerosismentioning

confidence: 99%