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      High density lipoproteins: Measurement techniques and potential biomarkers of cardiovascular risk

      review-article
      , *
      BBA Clinical
      Elsevier
      2D-PAGGE, two dimensional polyacrylamide gradient gel electrophoresis, ApoA-I, apolipoprotein A-I, CHD, coronary heart disease, CVD, cardiovascular disease, HDL, high density lipoprotein, HPLC, High Performance Liquid Chromatography, LCAT, lecithin–cholesterol acyltransferase, LDL, low density lipoprotein, MALDI, matrix-assisted laser desorption/ionization, MOP, myeloperoxidase, MS/MS, tandem-mass spectrometry, ND-PAGGE, non-denaturant polyacrylamide gradient gel electrophoresis, NMR, nuclear magnetic resonance, PEG, polyethylene glycol, PON1, paraoxonase 1, SELDI, surface enhanced laser desorption/ionization, TOF, time-of-flight, UTC, ultracentrifugation, Atherosclerosis, Coronary artery disease, High density lipoproteins, Apolipoprotein A-I, Cellular cholesterol efflux, Vascular endothelial function, Biomarkers of cardiovascular risk

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          Abstract

          Plasma high density lipoprotein cholesterol (HDL) comprises a heterogeneous family of lipoprotein species, differing in surface charge, size and lipid and protein compositions. While HDL cholesterol (C) mass is a strong, graded and coherent biomarker of cardiovascular risk, genetic and clinical trial data suggest that the simple measurement of HDL-C may not be causal in preventing atherosclerosis nor reflect HDL functionality. Indeed, the measurement of HDL-C may be a biomarker of cardiovascular health. To assess the issue of HDL function as a potential therapeutic target, robust and simple analytical methods are required. The complex pleiotropic effects of HDL make the development of a single measurement challenging. Development of laboratory assays that accurately HDL function must be developed validated and brought to high-throughput for clinical purposes. This review discusses the limitations of current laboratory technologies for methods that separate and quantify HDL and potential application to predict CVD, with an emphasis on emergent approaches as potential biomarkers in clinical practice.

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          MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data

          Background Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2. Results A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms. Conclusions MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses.
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            Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy.

            Laboratory measurements of plasma lipids (principally cholesterol and triglycerides) and lipoprotein lipids (principally low-density lipoprotein [LDL] and low-density lipoprotein [HDL] cholesterol) are the cornerstone of the clinical assessment and management of atherosclerotic cardiovascular disease (CVD) risk. LDL particles, and to a lesser extent very-low-density lipoprotein [VLDL] particles, cause atherosclerosis, whereas HDL particles prevent or reverse this process through reverse cholesterol transport. The overall risk for CVD depends on the balance between the "bad" LDL (and VLDL) and "good" HDL particles. Direct assessment of lipoprotein particle numbers us now possible through nuclear magnetic resonance spectroscopic analysis.
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              HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment

              Aims Niacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. Methods and results Prior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for ∼1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25% of participants allocated ERN/LRPT vs. 17% allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6–7.5; P 3× upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10%/year) ERN/LRPT vs. 30 (0.06%/year) placebo allocated participants. Conclusion The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ∼1 month, three-quarters continued to take it for ∼4 years.
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                Author and article information

                Contributors
                Journal
                BBA Clin
                BBA Clin
                BBA Clinical
                Elsevier
                2214-6474
                31 January 2015
                June 2015
                31 January 2015
                : 3
                : 175-188
                Affiliations
                McGill University Health Center, Royal Victoria Hospital, 687 Avenue des Pins West, Montreal, QC H3A 1A1, Canada
                Author notes
                [* ]Corresponding author. Tel.: + 1 514 934 1934x34642 or 36151; fax: + 1 514 843 2813. jacques.genest@ 123456mcgill.ca
                Article
                S2214-6474(15)00006-9
                10.1016/j.bbacli.2015.01.005
                4661556
                26674734
                eb6f1e84-51c1-4f3f-bc2a-de9bd687d95d
                © 2015 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 6 December 2014
                : 16 January 2015
                : 26 January 2015
                Categories
                Review

                2d-pagge, two dimensional polyacrylamide gradient gel electrophoresis,apoa-i, apolipoprotein a-i,chd, coronary heart disease,cvd, cardiovascular disease,hdl, high density lipoprotein,hplc, high performance liquid chromatography,lcat, lecithin–cholesterol acyltransferase,ldl, low density lipoprotein,maldi, matrix-assisted laser desorption/ionization,mop, myeloperoxidase,ms/ms, tandem-mass spectrometry,nd-pagge, non-denaturant polyacrylamide gradient gel electrophoresis,nmr, nuclear magnetic resonance,peg, polyethylene glycol,pon1, paraoxonase 1,seldi, surface enhanced laser desorption/ionization,tof, time-of-flight,utc, ultracentrifugation,atherosclerosis,coronary artery disease,high density lipoproteins,apolipoprotein a-i,cellular cholesterol efflux,vascular endothelial function,biomarkers of cardiovascular risk

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