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Mario Ruiz, Cecilia Frej, Andreas Holmér, Li J Guo, Sinh Tran, Björn Dahlbäck
OBJECTIVE: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Puhong Zhang, Jialin Gao, Chun Pu, Gang Feng, Lizhuo Wang, Lizhu Huang, Qingsong Tao, Yao Zhang
BACKGROUND: Apolipoprotein M (apoM) is mainly enriched in high-density lipoprotein (HDL) cholesterol and is slightly present in low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein cholesterol. apoM is involved in HDL formation and HDL-mediated reverse cholesterol transport. apoM is also associated with hyperlipidaemia and type 2 diabetes mellitus (T2DM). Significantly high plasma apoM levels are detected in hyperlipidaemia mice with a defective LDL receptor. By contrast, low plasma apoM levels are observed in patients with T2DM, which is often accompanied with hyperlipidaemia...
2016: Lipids in Health and Disease
Yaprak Engin-Üstün, Emel Kıyak Çağlayan, Ayşe Yeşim Göçmen, Muhammed Fevzi Polat
OBJECTIVES: The objective of this study was to describe the levels of chemerin, irisin and apolipoprotein M (apoM) in women with postmenopausal osteoporosis. METHODS: The study included 88 women with postmenopausal osteoporosis. Based on World Health Organization criteria, women with a T-score of ≤ -2.5 were defined as osteoporotic. In this case-control study, postmenopausal women with T-score > -1 were selected as controls (n = 88) and case-matched in a 1:1 ratio based on age (within 2 years) and body mass index (BMI) (within 1...
August 2016: Journal of Menopausal Medicine
Pu-Hong Zhang, Jia-Lin Gao, Chun Pu, Gang Feng, Li-Zhuo Wang, Li-Zhu Huang, Yao Zhang
BACKGROUND: Apolipoprotein M (apoM) was the carrier of the biologically active lipid mediator sphingosine-1-phospate in high density lipoprotein cholesterol (HDL-C) and played a critical role in formation and maturation of prebeta-HDL-C particles. The plasma apoM levels were decreased obviously in patients with type 2 diabetes mellitus (T2DM). A new single-nucleotide polymorphism (SNP) C-724del in apoM promoter was associated with a higher risk for coronary artery diseases (CAD) and myocardial infarction, could reduce promoter activities and apoM expression in vitro...
2016: Lipids in Health and Disease
Hansi Zhang, Kristyna Pluhackova, Zhenyan Jiang, Rainer A Böckmann
Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator carried by the HDL-associated apoM protein in blood, regulating many physiological processes by activating the G protein-coupled S1P receptor in mammals. Despite the solved crystal structure of the apoM-S1P complex, the mechanism of S1P release from apoM as a part of the S1P pathway is unknown. Here, the dynamics of the wild type apoM-S1P complex as well as of mutants were investigated by means of atomistic molecular dynamics simulations. The potential of mean force for S1P unbinding from apoM reflected a large binding strength of more than 60 kJ/mol...
2016: Scientific Reports
Jonathan K Fleming, Thomas R Glass, Steve J Lackie, Jonathan M Wojciak
Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are bioactive signaling lysophospholipids that activate specific G protein-coupled receptors on the cell surface triggering numerous biological events. In circulation, S1P and LPA associate with specific carrier proteins or chaperones; serum albumin binds both S1P and LPA while HDL shuttles S1P via interactions with apoM. We used a series of kinetic exclusion assays in which monoclonal anti-S1P and anti-LPA antibodies competed with carrier protein for the lysophospholipid to measure the equilibrium dissociation constants (Kd) for these carrier proteins binding S1P and the major LPA species...
September 2016: Journal of Lipid Research
Meiyong Li, Xinling Guo, Qiannan Li, Chongge You
Objective To investigate the relationship between the genetic polymorphisms of apolipoprotein M (ApoM) and the susceptibility to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) among Chinese Han population in Lanzhou. Methods Primers for the two single nucleotide polymorphism (SNP) sites (rs805296 and rs805297) in ApoM gene were designed and their genotyping methods of polymerase chain reaction-high resolution melting (PCR-HRM) assay were established. Case-control studies were performed among the 599 cases of RA, 194 cases of SLE, 179 cases of AS and 273 matched healthy controls to analyze the correlations between the two SNPs and the susceptibility to rheumatic diseases...
August 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Hsing-Chuan Tsai, May H Han
Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS)...
July 2016: Drugs
Abrar Ahmad, Kristina Sundquist, Bengt Zöller, Björn Dahlbäck, Peter J Svensson, Jan Sundquist, Ashfaque A Memon
Apolipoprotein M (ApoM) plasma levels have been reported to be associated with risk of venous thromboembolism (VTE) recurrence. However, the role of genetic alterations in the ApoM gene in VTE recurrence remains unknown. The aim of this study was to identify genetic aberrations in ApoM gene in VTE recurrence and their role in prediction of VTE recurrence in a prospective follow-up study of 1465 VTE patients. During follow-up, 156 (10.6 %) patients had VTE recurrence. First screening of whole ApoM gene was performed by Sanger's sequencing in selected age and sex matched non-recurrent and recurrent patients (n=95)...
August 30, 2016: Thrombosis and Haemostasis
Jorie Versmissen, Ranitha Vongpromek, Reyhana Yahya, Jeroen B van der Net, Leonie van Vark-van der Zee, Jeannette Blommesteijn-Touw, Darcos Wattimena, Trinet Rietveld, Clive R Pullinger, Christina Christoffersen, Björn Dahlbäck, John P Kane, Monique Mulder, Eric J G Sijbrands
BACKGROUND: Coronary heart disease (CHD) risk inversely associates with levels of high-density lipoprotein cholesterol (HDL-C). The protective effect of HDL is thought to depend on its functionality, such as its ability to induce cholesterol efflux. MATERIALS AND METHODS: We compared plasma cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM)...
July 2016: European Journal of Clinical Investigation
Shengyu Tan, Xianling Liu, Yan Xu, Lu Luo, Shenghua Zhou, Yawen Gao
PURPOSE: The purpose of this study was to investigate the correlation between serum levels of serum apolipoprotein M (ApoM), A5 (ApoA5), and high-density lipoprotein (HDL) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and study the effects of nasal continuous positive airway pressure treatment on these serum biomarkers. METHODS: Thirty OSAHS patients and 15 non-OSAHS probands as control were selected for the study. Serum HDL, ApoM, and ApoA5 levels in two groups were detected; differences and association among them were analyzed...
May 21, 2016: Sleep & Breathing, Schlaf & Atmung
Hui Li, Yinyin Liu, Ling Wang, Ting Shen, Wenhan Du, Zhijun Liu, Ruohong Chen, Min Hu
BACKGROUND: Recently, variations in a component of high-density lipoprotein (HDL), namely apolipoprotein M (apoM), were found to be associated with chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the association between apoM and COPD severity. Factors associated with apoM, COPD, or coronary artery disease (CAD) were also assessed. METHODS: A total of 110 COPD patients and 110 age- and sex-matched non-COPD controls were included...
2016: Lipids in Health and Disease
Thomas A Hughes, Rossana M Calderon, Sylvia Diaz, Armando J Mendez, Ronald B Goldberg
OBJECTIVE: High cardiovascular mortality in patients with type 1 diabetes (T1DM) is widely recognized. Paradoxically, these patients have been shown to have elevated HDL-C and reduced apoB-containing lipoproteins. The purpose of this investigation was to further characterize the lipoprotein composition in T1DM and to assess the role that lipases and adipokines may play in these differences. METHODS: T1DM patients (89) attending the Diabetes Clinic at the University of Miami and 42 healthy controls were recruited...
May 2016: Journal of Diabetes and its Complications
Cecilia Frej, Adam Linder, Kaisa E Happonen, Fletcher B Taylor, Florea Lupu, Björn Dahlbäck
Sphingosine 1-phosphate (S1P) is an important regulator of vascular integrity and immune cell migration, carried in plasma by high-density lipoprotein (HDL)-associated apolipoprotein M (apoM) and by albumin. In sepsis, the protein and lipid composition of HDL changes dramatically. The aim of this study was to evaluate changes in S1P and its carrier protein apoM during sepsis. For this purpose, plasma samples from both human sepsis patients and from an experimental Escherichia coli sepsis model in baboons were used...
June 2016: Journal of Cellular and Molecular Medicine
Pernille M Christensen, Catherine H Liu, Steven L Swendeman, Hideru Obinata, Klaus Qvortrup, Lars B Nielsen, Timothy Hla, Annarita Di Lorenzo, Christina Christoffersen
Apolipoprotein M (ApoM) transports sphingosine-1-phosphate (S1P) in plasma, and ApoM-deficient mice (Apom(-/-)) have ∼50% reduced plasma S1P levels. There are 5 known S1P receptors, and S1P induces adherens junction formation between endothelial cells through the S1P1 receptor, which in turn suppresses vascular leak. Increased vascular permeability is a hallmark of inflammation. The purpose of this study was to explore the relationships between vascular leakage in ApoM deficiency and S1P1 function in normal physiology and in inflammation...
June 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Alessandra di Masi, Viviana Trezza, Loris Leboffe, Paolo Ascenzi
Lipocalins are an evolutionarily conserved family of proteins that bind and transport a variety of exogenous and endogenous ligands. Lipocalins share a conserved eight anti-parallel β-sheet structure. Among the different lipocalins identified in humans, α-1-acid glycoprotein (AGP), apolipoprotein D (apoD), apolipoprotein M (apoM), α1-microglobulin (α1-m) and retinol-binding protein (RBP) are plasma proteins. In particular, AGP is the most important transporter for basic and neutral drugs, apoD, apoM, and RBP mainly bind endogenous molecules such as progesterone, pregnenolone, bilirubin, sphingosine-1-phosphate, and retinol, while α1-m binds the heme...
April 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Payam Emami Khoonsari, Anna Häggmark, Maria Lönnberg, Maria Mikus, Lena Kilander, Lars Lannfelt, Jonas Bergquist, Martin Ingelsson, Peter Nilsson, Kim Kultima, Ganna Shevchenko
Alzheimer's disease is a neurodegenerative disorder accounting for more than 50% of cases of dementia. Diagnosis of Alzheimer's disease relies on cognitive tests and analysis of amyloid beta, protein tau, and hyperphosphorylated tau in cerebrospinal fluid. Although these markers provide relatively high sensitivity and specificity for early disease detection, they are not suitable for monitor of disease progression. In the present study, we used label-free shotgun mass spectrometry to analyse the cerebrospinal fluid proteome of Alzheimer's disease patients and non-demented controls to identify potential biomarkers for Alzheimer's disease...
2016: PloS One
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
Weiying Gu, Lili Xiang, Tingxiu Jiang, Guanghua Luo, Jiang Wei, Jiannong Cen, Zixing Chen, Guoqiang Qiu, Mei Zeng, Xiaoying Zhang
We examined the effect of simvastatin (SV) alone and in combination with all-trans retinoic acid (ATRA) on proliferation, differentiation, apoptosis and apolipoprotein M (apoM) expression in the human promyelocytic leukemia cell line NB4. The NB4 cells were incubated with 10 μM Simvastatin (10SV) and 0.5 μM ATRA alone or in combination, taking NB4 cells without any treatment as normal controls. The cells of different groups were collected at 24, 48 and 72 h post-incubation for further detection. Their morphological changes were observed after Wright stain...
March 2016: Indian Journal of Hematology & Blood Transfusion
Sandrine Morel, Christina Christoffersen, Lene N Axelsen, Fabrizio Montecucco, Viviane Rochemont, Miguel A Frias, Francois Mach, Richard W James, Christian C Naus, Marc Chanson, Paul D Lampe, Morten S Nielsen, Lars B Nielsen, Brenda R Kwak
AIM: Increasing evidence points to lipoprotein composition rather than reverse cholesterol transport in the cardioprotective properties of high-density lipoproteins (HDLs). HDL binding to receptors at the surface of cardiomyocytes activates signalling pathways promoting survival, but downstream targets are largely unknown. Here, we investigate the pathways by which the sphingosine-1-phosphate (S1P) constituent of HDL limits cell death induced by cardiac ischaemia-reperfusion (I/R). METHODS AND RESULTS: Apolipoprotein M (ApoM) transgenic (Apom-Tg) mice, in which plasma S1P is increased by 296%, and wild-type (WT) mice were subjected to in vivo I/R...
March 1, 2016: Cardiovascular Research
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