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HDL Proteomics

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
Sasha A Singh, Allison B Andraski, Brett Pieper, Wilson Goh, Carlos O Mendivil, Frank M Sacks, Masanori Aikawa
Endogenous labeling with stable isotopes is used to study the metabolism of proteins in vivo. However, traditional detection methods such as GC/MS cannot measure tracer enrichment in multiple proteins simultaneously, and multiple reaction monitoring MS cannot measure precisely the low tracer enrichment in slowly turning-over proteins as in HDL. We exploited the versatility of the high-resolution/accurate mass (HR/AM) quadrupole Orbitrap for proteomic analysis of five HDL sizes. We identified 58 proteins in HDL that were shared among three humans and that were organized into five subproteomes according to HDL size...
April 2016: Journal of Lipid Research
Margery A Connelly, Irina Shalaurova, James D Otvos
Great advances are being made at the mechanistic level in the understanding of the structural and functional diversity of high-density lipoprotein (HDL). HDL particle subspecies of different sizes are now known to differ in the protein and lipid cargo they transport, conferring on them the ability to perform different functions that in aggregate would be expected to provide protection against the development of atherosclerosis and its downstream clinical consequences. Exacerbating what is already a very complex system is the finding that inflammation, via alteration of the proteomic and lipidomic composition of HDL subspecies, can modulate at least some of their functional activities...
July 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Manja Koch, Majken K Jensen
PURPOSE OF REVIEW: Dementia is a major cause of disability and institutionalization. Apart from age and apolipoprotein E (APOE) genotype, there are currently no established, clinically relevant, noninvasive markers of dementia. We conducted a literature search of recent observational epidemiological studies evaluating the relevance of HDL cholesterol (HDL-C) and apolipoproteins as biomarkers of future and prevalent risk of dementia. RECENT FINDINGS: HDL-C and apolipoproteins, such as apoE have been suggested to play important roles in brain function and have been associated with dementia and Alzheimer's disease in observational studies...
February 2016: Current Opinion in Lipidology
Andreas Oberbach, Volker Adams, Nadine Schlichting, Marco Heinrich, Yvonne Kullnick, Stefanie Lehmann, Sven Lehmann, Stefan Feder, Joao Carlos Correia, Friedrich-Wilhelm Mohr, Uwe Völker, Nico Jehmlich
Besides modulation of reverse cholesterol transport, high density lipoprotein (HDL) is able to modulate vascular function by stimulating endothelial nitric oxide synthase. Recently, it could be documented that this function of HDL was significantly impaired in patients with chronic heart failure (CHF). We investigated alterations in the HDL proteome in CHF patients. Therefore, HDL was isolated from 5 controls (HDLhealthy) and 5 CHF patients of NYHA-class IIIb (HDLCHF). Proteome analysis of HDL particles was performed by two-dimensional liquid chromatography-mass spectrometry (SCX/RP LC-MS/MS)...
January 30, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Nathalie Pamir, Patrick Hutchins, Graziella Ronsein, Tomas Vaisar, Catherine A Reardon, Godfrey S Getz, Aldons J Lusis, Jay W Heinecke
Cholesterol efflux capacity associates strongly and negatively with the incidence and prevalence of human CVD. We investigated the relationships of HDL's size and protein cargo with its cholesterol efflux capacity using APOB-depleted serum and HDLs isolated from five inbred mouse strains with different susceptibilities to atherosclerosis. Like humans, mouse HDL carried >70 proteins linked to lipid metabolism, the acute-phase response, proteinase inhibition, and the immune system. HDL's content of specific proteins strongly correlated with its size and cholesterol efflux capacity, suggesting that its protein cargo regulates its function...
February 2016: Journal of Lipid Research
Juan Salazar, Luis Carlos Olivar, Eduardo Ramos, Mervin Chávez-Castillo, Joselyn Rojas, Valmore Bermúdez
High-Density Lipoprotein-Cholesterol (HDL-C) is regarded as an important protective factor against cardiovascular disease, with abundant evidence of an inverse relationship between its serum levels and risk of cardiovascular disease, as well as various antiatherogenic, antioxidant, and anti-inflammatory properties. Nevertheless, observations of hereditary syndromes featuring scant HDL-C concentration in absence of premature atherosclerotic disease suggest HDL-C levels may not be the best predictor of cardiovascular disease...
2015: Cholesterol
A Herosimczyk, A Lepczyński, M Ożgo, J Skomiał, A Dratwa-Chałupnik, A Tuśnio, M Taciak, M Barszcz
In the present study we introduced a two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation time of flight mass spectrometry-based proteomic workflow to identify proteins that show altered expression as a result of the addition of 2% of water extract of inulin-type fructans to the diet of growing piglets. This analysis allowed us to detect an average of 240 spots per gel with a mass range from 10 to 250 kDa and a pH ranging from 3 to 10. Twenty protein spots were found to show statistically significant differences in their expression...
2015: Polish Journal of Veterinary Sciences
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