| 1. |
- Svensson, Per Anders, 1959, et al.
(författare)
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Identification of genes predominantly expressed in human macrophages
- 2004
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Ingår i: Atherosclerosis. - : Elsevier BV. ; 177, s. 287-290
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Tidskriftsartikel (refereegranskat)abstract
- Identification of cell and tissue specific genes may provide novel insights to signaling systems and functions. Macrophages play a key role in many diseases including atherosclerosis. Using DNA microarrays we compared the expression of approximately 10,000 genes in 56 human tissues and identified 23 genes with predominant expression in macrophages. The identified genes include both genes known to be macrophage specific and genes previously not well described in this cell type. Tissue distribution of two genes, liver X receptor (LXR) alpha and interleukin-1 receptor antagonist (IL1RN), was verified by real-time RT-PCR. We conclude that comparison of expression profiles from a large number of tissues can be used to identify genes that are predominantly expressed in certain tissues. Identification of novel macrophage specific genes may increase our understanding of the role of this cell in different diseases.
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| 2. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
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Ingår i: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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| 3. |
- Fryk, Emanuel, et al.
(författare)
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Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients
- 2016
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Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:7, s. 998-1006
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p < 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p < 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p < 0.05) and increased by overfeeding (p < 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p < 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.
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| 4. |
- Aspenberg, Per, 1949-, et al.
(författare)
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Artrosskolan : evidensen måste stärkas
- 2018
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 115
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 5. |
- Boström, Pontus, 1982, et al.
(författare)
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The SNARE protein SNAP23 and the SNARE-interacting protein Munc18c in human skeletal muscle are implicated in insulin resistance/type 2 diabetes.
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 59:8, s. 1870-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes. The objective was to determine whether SNAP23 may also be involved in the known association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23. RESEARCH DESIGN AND METHODS: We analyzed skeletal muscle biopsies from patients with type 2 diabetes and healthy, insulin-sensitive control subjects for expression (mRNA and protein) and intracellular localization (subcellular fractionation and immunohistochemistry) of SNAP23, and for expression of proteins known to interact with SNARE proteins. Insulin resistance was determined by a euglycemic hyperinsulinemic clamp. Potential mechanisms for regulation of SNAP23 were also investigated in the skeletal muscle cell line L6. RESULTS: We showed increased SNAP23 levels in skeletal muscle from patients with type 2 diabetes compared with that from lean control subjects. Moreover, SNAP23 was redistributed from the plasma membrane to the microsomal/cytosolic compartment in the patients with the type 2 diabetes. Expression of the SNARE-interacting protein Munc18c was higher in skeletal muscle from patients with type 2 diabetes. Studies in L6 cells showed that Munc18c promoted the expression of SNAP23. CONCLUSIONS: We have translated our previous in vitro results into humans by showing that there is a change in the distribution of SNAP23 to the interior of the cell in skeletal muscle from patients with type 2 diabetes. We also showed that Munc18c is a potential regulator of SNAP23.
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| 6. |
- Jernås, Margareta, 1961, et al.
(författare)
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Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression
- 2006
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Ingår i: The FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Enlarged adipocytes are associated with insulin resistance and are an independent predictor of type 2 diabetes. To understand the molecular link between these diseases and adipocyte hypertrophy, we developed a technique to separate human adipocytes from an adipose tissue sample into populations of small cells (mean 57.6+-3.54 um) and large cells (mean 100.1+-3.94 um). Microarray analysis of the cell populations separated from adipose tissue from three subjects identified 14 genes, of which five immune-related, with more than fourfold higher expression in large cells than small cells. Two of these genes were serum amyloid A (SAA) and transmembrane 4 L six family member 1 (TM4SF1). Real-time RT-PCR analysis of SAA and TM4SF1 expression in adipocytes from seven subjects revealed 19-fold and 22-fold higher expression in the large cells, respectively, and a correlation between adipocyte size and both SAA and TM4SF1 expression. The results were verified using immunohistochemistry. In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression. Thus, we have identified genes with markedly higher expression in large, compared with small, human adipocytes. These genes may link hypertrophic obesity to insulin resistance/type 2 diabetes.
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| 7. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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