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HDL Proteomics

Ashley N Williams, Baqiyyah N Conway
Findings of increased hemoglobin inside the HDL proteome among persons with diabetes who have haptoglobin 2-2 genotype suggest that iron-induced lipid peroxidation may be involved in diabetic kidney disease. We investigated the relationships of serum hemoglobin and iron with kidney function, and whether this varied by level of HDLc, in 5296 adults with and 49,161 without diabetes. Estimated eGFR was our marker of kidney function. Hemoglobin was positively associated with eGFR among those with diabetes and inversely among those without diabetes (interaction p-value <0...
March 29, 2017: Journal of Diabetes and its Complications
Debi K Swertfeger, Hailong Li, Sandra Rebholz, Xiaoting Zhu, Amy S Shah, W Sean Davidson, Long J Lu
HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS)...
April 2017: Molecular & Cellular Proteomics: MCP
Raimund Pechlaner, Sotirios Tsimikas, Xiaoke Yin, Peter Willeit, Ferheen Baig, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Joseph L Witztum, Veronica J Alexander, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD. OBJECTIVES: This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome...
February 21, 2017: Journal of the American College of Cardiology
Sasha A Singh, Masanori Aikawa
PURPOSE OF REVIEW: Mass spectrometry is an ever evolving technology that is equipped with a variety of tools for protein research. Some lipoprotein studies, especially those pertaining to HDL biology, have been exploiting the versatility of mass spectrometry to understand HDL function through its proteome. Despite the role of mass spectrometry in advancing research as a whole, however, the technology remains obscure to those without hands on experience, but still wishing to understand it...
February 2017: Current Opinion in Lipidology
Kaijie Xiao, Fan Yu, Zhixin Tian
For top-down protein database search and identification from tandem mass spectra, our isotopic envelope fingerprinting search algorithm and ProteinGoggle search engine have demonstrated their strength of efficiently resolving heavily overlapping data as well separating non-ideal data with non-ideal isotopic envelopes from ideal ones with ideal isotopic envelopes. Here we report our updated ProteinGoggle 2.0 for intact protein database search with full-capacity. The indispensable updates include users' optional definition of dynamic post-translational modifications and static chemical labeling during database creation, comprehensive dissociation methods and ion series, as well as a Proteoform Score for each proteoform...
January 30, 2017: Journal of Proteomics
Elena Burillo, Inmaculada Jorge, Diego Martínez-López, Emilio Camafeita, Luis Miguel Blanco-Colio, Marco Trevisan-Herraz, Iakes Ezkurdia, Jesús Egido, Jean-Baptiste Michel, Olivier Meilhac, Jesús Vázquez, Jose Luis Martin-Ventura
High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma)...
December 9, 2016: Scientific Reports
Michael Holzer, Sabine Kern, Ruth Birner-Grünberger, Sanja Curcic, Akos Heinemann, Gunther Marsche
Proteomics have extended the list of high-density lipoprotein (HDL) associated proteins to about 90. One of the major issues of global protein characterization is establishing specificity of association as opposed to contamination, a fact which has never been addressed for isolated HDL. We have developed a refined purification strategy to isolate HDL by density, followed by purification by size to generate "highly purified" fractions of HDL2/3, which allow the reliable quantification of the HDL proteome for biomarker discovery...
December 5, 2016: Scientific Reports
Stefan A Ljunggren, Ingela Helmfrid, Ulf Norinder, Mats Fredriksson, Gun Wingren, Helen Karlsson, Mats Lindahl
There is a growing body of evidence that persistent organic pollutants (POPs) may increase the risk for cardiovascular disease (CVD), but the mechanisms remain unclear. High-density lipoprotein (HDL) acts protective against CVD by different processes, and we have earlier found that HDL from subjects with CVD contains higher levels of POPs than healthy controls. In the present study, we have expanded analyses on the same individuals living in a contaminated community and investigated the relationship between the HDL POP levels and protein composition/function...
November 16, 2016: Environment International
Magdalena Luczak, Dorota Formanowicz, Łukasz Marczak, Joanna Suszyńska-Zajczyk, Elżbieta Pawliczak, Maria Wanic-Kossowska, Maciej Stobiecki
Patients with chronic kidney disease (CKD) have a considerably higher risk of death due to cardiovascular causes. Using an iTRAQ MS/MS approach, we investigated the alterations in plasma protein accumulation in patients with CKD and classical cardiovascular disease (CVD) without CKD. The proteomic analysis led to the identification of 130 differentially expressed proteins among CVD and CKD patients and healthy volunteers. Bioinformatics analysis revealed that 29 differentially expressed proteins were involved in lipid metabolism and atherosclerosis, 20 of which were apolipoproteins and constituents of high-density lipoprotein (HDL) and low-density lipoprotein (LDL)...
2016: Scientific Reports
Shankarappa Manjunatha, Klaus Distelmaier, Surendra Dasari, Rickey E Carter, Yogish C Kudva, K Sreekumaran Nair
OBJECTIVE: Higher HDL-cholesterol (HDL-C) is linked to lower cardiovascular risk but individuals with type 1 diabetes mellitus (T1DM) with normal or high HDL-C have higher cardiovascular events compared to age matched non-diabetic controls (ND). We determined whether altered HDL functions despite having normal HDL-C concentration may explain increased cardiovascular risk in T1DM individuals. We also determined whether irreversible posttranslational modifications (PTMs) of HDL bound proteins occur in T1DM individuals with altered HDL functions...
September 2016: Metabolism: Clinical and Experimental
Scott M Gordon, Hailong Li, Xiaoting Zhu, Patrick Tso, Catherine A Reardon, Amy S Shah, L Jason Lu, W Sean Davidson
UNLABELLED: Given their association with cardiovascular disease protection, there has been intense interest in understanding the biology of high density lipoproteins (HDL). HDL is actually a family of diverse particle types, each made up of discrete - but as yet undetermined - combinations of proteins drawn from up to 95 lipophilic plasma proteins. The abundant apolipoproteins (apo) of the A class (apoA-I, apoA-II and apoA-IV) have been proposed to act as organizing platforms for auxiliary proteins, but this concept has not been systematically evaluated...
September 2, 2016: Journal of Proteomics
Christine von Toerne, Cornelia Huth, Tonia de Las Heras Gala, Florian Kronenberg, Christian Herder, Wolfgang Koenig, Christa Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Michael Roden, Annette Peters, Barbara Thorand, Stefanie M Hauck
AIMS/HYPOTHESIS: Individuals at a high risk of type 2 diabetes demonstrate moderate impairments in glucose metabolism years before the clinical manifestation of type 2 diabetes, a state called 'prediabetes'. In order to elucidate the pathophysiological processes leading to type 2 diabetes, we aimed to identify protein biomarkers associated with prediabetes. METHODS: In a proteomics study, we used targeted selected reaction monitoring (SRM)-MS to quantify 23 candidate proteins in the plasma of 439 randomly selected men and women aged 47-76 years from the population-based German KORA F4 study...
September 2016: Diabetologia
Joanna Godzien, Michal Ciborowski, Emily Grace Armitage, Inmaculada Jorge, Emilio Camafeita, Elena Burillo, Jose Luis Martín-Ventura, Francisco J Rupérez, Jesús Vázquez, Coral Barbas
A single in-vial dual extraction (IVDE) procedure for the subsequent analysis of lipids and proteins in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions derived from the same biological sample is presented. On the basis of methyl-tert-butyl ether (MTBE) extraction, IVDE leads to the formation of three phases: a protein pellet at the bottom, an aqueous phase with polar compounds, and an ether phase with lipophilic compounds. After sample extraction, performed within a high-performance liquid chromatography vial insert, the ether phase was directly injected for lipid fingerprinting, while the protein pellet, after evaporation of the remaining sample, was used for proteomics analysis...
June 3, 2016: Journal of Proteome Research
Judit Cubedo, Teresa Padró, Rodrigo Alonso, Pedro Mata, Lina Badimon
HDL composition rather than HDL-cholesterol (HDL-C) levels seems to be a key determinant of HDL-induced atheroprotection. Heterozygous familial hypercholesterolemia (FH) patients, with lifelong exposure to high LDL levels, show a high prevalence of premature coronary artery disease. We hypothesized that HDL of FH patients might have a modified protein composition and investigated the proteomic signature of HDL obtained from FH patients and their unaffected relatives. HDLs were characterized by 2D electrophoresis/MS in 10 families from the SAFEHEART cohort (3 individuals/family: 2 with genetic FH diagnosis and 1 non-FH relative) clinically characterized and treated as per guidelines...
June 2016: Journal of Lipid Research
Markus Trieb, Angela Horvath, Ruth Birner-Gruenberger, Walter Spindelboeck, Vanessa Stadlbauer, Ulrike Taschler, Sanja Curcic, Rudolf E Stauber, Michael Holzer, Lisa Pasterk, Akos Heinemann, Gunther Marsche
High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls...
July 2016: Biochimica et Biophysica Acta
Marcella O'Reilly, Eugene Dillon, Weili Guo, Orla Finucane, Aoibheann McMorrow, Aoife Murphy, Claire Lyons, Daniel Jones, Miriam Ryan, Michael Gibney, Eileen Gibney, Lorraine Brennan, Margarita de la Llera Moya, Muredach P Reilly, Helen M Roche, Fiona C McGillicuddy
BACKGROUND: Acute inflammation impairs reverse cholesterol transport (RCT) and reduces high-density lipoprotein (HDL) function in vivo. This study hypothesized that obesity-induced inflammation impedes RCT and alters HDL composition, and investigated if dietary replacement of saturated (SFA) for monounsaturated (MUFA) fatty acids modulates RCT. METHODS AND RESULTS: Macrophage-to-feces RCT, HDL efflux capacity, and HDL proteomic profiling was determined in C57BL/6j mice following 24 weeks on SFA- or MUFA-enriched high-fat diets (HFDs) or low-fat diet...
May 10, 2016: Circulation
Weilie Ma, Margarita Lin, Hang Ding, Guorong Lin, Zhizhen Zhang
OBJECTIVE: HDL and its apolipoproteins protect against atherosclerotic disease partly by removing excess cholesterol from macrophage foam cells. But the underlying mechanisms of cholesterol clearance are still not well defined. We investigated roles of vesicle trafficking of coatomer β-COP in delivering cholesterol to the cell surface during apoA-1 and apoE-mediated lipid efflux from fibroblasts and THP-1 macrophages. METHODS: shRNA knockout, confocal and electron microscopy and biochemical analysis were used to investigate the roles of β-COP in apolipoprotein-mediated cholesterol efflux in fibroblasts and THP-1 macrophages...
2016: PloS One
Ruomeng Li, Linlin Zhao, Ning Wu, Ruiyi Wang, Xin Cao, Xinjian Qiu, Dongsheng Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Yinchenwuling Powder (YCL) is a traditional Chinese medicine formula originated from Synopsis of Golden Chamber, which is effective in positively modulating lipid levels in clinics. In this study, we utilized proteomic technology to identify the therapeutic targets of YCL on hyperlipidemic rats. METHODS: We established hyperlipidemic model rats and administrated them with different doses of YCL extracts (0.35g/ml, 0.75g/ml and 1.5g/ml)...
June 5, 2016: Journal of Ethnopharmacology
Robert S Rosenson
Classical epidemiology has established the incremental contribution of the high-density lipoprotein (HDL) cholesterol measure in the assessment of atherosclerotic cardiovascular disease risk; yet, genetic epidemiology does not support a causal relationship between HDL cholesterol and the future risk of myocardial infarction. Therapeutic interventions directed toward cholesterol loading of the HDL particle have been based on epidemiological studies that have established HDL cholesterol as a biomarker of atherosclerotic cardiovascular risk...
May 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Clark M Henderson, Tomas Vaisar, Andrew N Hoofnagle
The sensitivity and specificity of tandem mass spectrometers have made targeted proteomics the method of choice for the precise simultaneous measurement of many proteins in complex mixtures. Its application to the relative quantification of proteins in high-density lipoproteins (HDL) that have been purified from human plasma has revealed potential mechanisms to explain the atheroprotective effects of HDL. We describe a moderate throughput method for isolating HDL from human plasma that uses sequential density gradient ultracentrifugation, the traditional method of HDL purification, and subsequent trypsin digestion and nanoflow liquid chromatography-tandem mass spectrometry to quantify 38 proteins in the HDL fraction of human plasma...
2016: Methods in Molecular Biology
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