| 1. |
- Bennermo, Marie, et al.
(författare)
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Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction : a case-control study
- 2011
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Ingår i: Journal of Interferon and Cytokine Research. - : Mary Ann Liebert Inc. - 1079-9907 .- 1557-7465. ; 31:2, s. 259-264
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.
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| 2. |
- Edsgärd, Daniel, et al.
(författare)
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GeneiASE : Detection of condition-dependent and static allele-specific expression from RNA-seq data without haplotype information
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition-dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively.
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| 3. |
- Kovacs, Alexander, et al.
(författare)
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Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 104:34, s. 13768-13773
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Tidskriftsartikel (refereegranskat)abstract
- Increased baseline values of the acute-phase reactant C-reactive protein (CRP) are significantly associated with future cardiovascular disease, and some in vitro studies have claimed that human CRP (hCRP) has proatherogenic effects. In vivo studies in apolipoprotein E-deficient mouse models, however, have given conflicting results. We bred atherosclerosis-prone mice (Apob 100/100Ldlr-/-), which have human-like hypercholesterolemia, with hCRP transgenic mice (hCRP+/0) and studied lesion development at 15, 30, 40, and 50 weeks of age. Atherosclerotic lesions were smaller in hCRP+/0 Apob100/100Ldlr-/- mice than in hCRP0/0Apob100/100Ldlr-/- controls, as judged from the lesion surface areas of pinned-out aortas from mice at 40 and 50 weeks of age. In lesions from 40-week-old mice, mRNA expression levels of several genes in the proteasome degradation pathway were higher in hCRP +/0Apob100/100Ldlr-/- mice than in littermate controls, as shown by global gene expression profiles. These results were confirmed by real-time PCR, which also indicated that the activities of those genes were the same at 30 and 40 weeks in hCRP+/0Apob 100/100Ldlr-/- mice but were significantly lower at 40 weeks than at 30 weeks in controls. Our results show that hCRP is not proatherogenic but instead slows atherogenesis, possibly through proteasome-mediated protein degradation. © 2007 by The National Academy of Sciences of the USA.
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| 4. |
- Lundman, Pia, et al.
(författare)
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A high-fat meal is accompanied by increased plasma interleukin-6 concentrations
- 2007
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 17:3, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Enhanced and prolonged postprandial lipaemia is associated with coronary heart disease (CHD). However, the mechanisms linking postprandial lipaemia to the increased risk of atherosclerosis and CHD remain to be determined. The aim of the present study was to examine the effects of a high-fat meal on plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and cellular adhesion molecules in CHD patients and control subjects. METHODS AND RESULTS: Forty-one middle-aged men with premature CHD and 26 healthy male controls were investigated. The plasma triglyceride response to the high-fat meal was significantly greater among cases than controls. The oral fat load induced a twofold increase in plasma concentrations of IL-6, an increase that was similar in CHD patients and control subjects. No changes could be detected in plasma concentrations of cellular adhesion molecules in response to postprandial lipaemia in either CHD patients or control subjects. CONCLUSION: The results of the present study suggest that a high-fat meal affects mechanisms that induce increased inflammatory activity, which is recognised as a key modulator in the development of atherosclerosis and CHD. However, the increased levels of plasma IL-6 appear not to be determined by the magnitude of the postprandial triglyceridaemia.
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