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| 2. |
- 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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| 3. |
- Happe, Anne-Kathrin, et al.
(författare)
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Predatory arthropods in apple orchards across Europe : Responses to agricultural management, adjacent habitat, landscape composition and country
- 2019
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Ingår i: Agriculture, Ecosystems & Environment. - : Elsevier BV. - 0167-8809 .- 1873-2305. ; 273, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Local agri-environmental schemes, including hedgerows, flowering strips, organic management, and a landscape rich in semi-natural habitat patches, are assumed to enhance the presence of beneficial arthropods and their contribution to biological control in fruit crops. We studied the influence of local factors (orchard management and adjacent habitats) and of landscape composition on the abundance and community composition of predatory arthropods in apple orchards in three European countries. To elucidate how local and landscape factors influence natural enemy effectiveness in apple production systems, we calculated community energy use as a proxy for the communities' predation potential based on biomass and metabolic rates of predatory arthropods. Predator communities were assessed by standardised beating samples taken from apple trees in 86 orchards in Germany, Spain and Sweden. Orchard management included integrated production (IP; i.e. the reduced and targeted application of synthetic agrochemicals), and organic management practices in all three countries. Predator communities differed between management types and countries. Several groups, including beetles (Coleoptera), predatory bugs (Heteroptera), flies (Diptera) and spiders (Araneae) benefited from organic management depending on country. Woody habitat and IP supported harvestmen (Opiliones). In both IP and organic orchards we detected aversive influences of a high-quality surrounding landscape on some predator groups: for example, high covers of woody habitat reduced earwig abundances in German orchards but enhanced their abundance in Sweden, and high natural plant species richness tended to reduce predatory bug abundance in Sweden and IP orchards in Spain. We conclude that predatory arthropod communities and influences of local and landscape factors are strongly shaped by orchard management, and that the influence of management differs between countries. Our results indicate that organic management improves the living conditions for effective predator communities.
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| 4. |
- Hägg, Sara, 1977-, et al.
(författare)
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Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2 : The Stockholm Atherosclerosis Gene Expression (STAGE) Study
- 2009
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Ingår i: PLoS Genetics. - : PLoS Genetics. - 1553-7390 .- 1553-7404. ; 5:12, s. e1000754-
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n=66/tissue) and atherosclerotic and unaffected arterial wall (n=40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n=15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n=3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n=49/48) and one visceral fat (n=59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P=0.008 and P=0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n=55/54) relating to carotid stenosis (P=0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n=16/17, P<10-27and-30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, cellular and lesion expression of LDB2, and the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and together with LDB2 merits further attention in CAD research.
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| 6. |
- Krivospitskaya, Olesya, 1983-, et al.
(författare)
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A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis
- 2012
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Ingår i: Molecular Medicine. - New York, USA : The Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 18:1, s. 712-718
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Tidskriftsartikel (refereegranskat)abstract
- All-trans retinoic acid, controlled by CYP26 enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26B1 in atherosclerosis and effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries and CYP26B1 and the macrophage marker CD68 co-localized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic than normal arteries. Databases were queried for non-synonymous CYP26B1 SNPs and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophage-like cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.
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| 7. |
- 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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| 8. |
- Malarstig, A., et al.
(författare)
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Plasma CD93 concentration is a potential novel biomarker for coronary artery disease
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 270:3, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. A common nonsynonymous single nucleotide polymorphism (SNP) in the CD93 gene (rs3746731, Pro541Ser) has been associated with risk of coronary artery disease (CAD). CD93 is a transmembrane glycoprotein, which is detectable in soluble form in human plasma. We investigated whether the concentration of soluble CD93 in plasma is related to risk of myocardial infarction (MI) and CAD, using a case-control study of premature MI (n = 764) and a nested case-control analysis of a longitudinal cohort study of 60-year-old subjects (analysis comprising 844 of 4232 subjects enrolled at baseline). In addition, SNPs in the CD93 gene were studied in relation to plasma CD93 concentration and CD93 mRNA expression. Methods and Results. A sensitive and specific enzyme-linked immunosorbent assay was established for determination of the plasma CD93 concentration. Subjects were divided into three groups according to tertiles of the distribution of CD93 concentration. Lower odds ratios for risk of MI and incidence of CAD were observed in the middle CD93 tertile (142-173 mu g L(-1)): odds ratio (95% confidence interval), 0.69 (0.49-0.97) and 0.61 (0.40-0.94), respectively. These associations were independent of traditional CAD risk factors. The minor allele of a SNP in the 3' untranslated region of CD93(rs2749812) was associated with increased plasma CD93 concentrations (P = 0.03) and increased CD93 mRNA expression levels (P = 0.02). Conclusion. The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.
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| 9. |
- Samnegård, Ann
(författare)
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Inflammation and matrix degrading proteases in coronary artery disease
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Coronary artery disease (CAD) is a major cause of morbidity and death in the world today. The underlying process, atherosclerosis, is caused by lipid accumulation and inflammatory processes within the intimal layer of the vessel wall. Stable CAD is characterized by gradually expanding atherosclerotic plaques that narrow the lumen and, by restricting the blood flow, give rise to ischemic symptoms. Acute coronary syndromes (ACS) are usually caused by vulnerable plaques, which rupture or erode, thus initiating thrombus formation that suddenly impairs the blood flow and may cause acute myocardial infarction (MI). Inflammation is now considered to be an important feature of both atherosclerosis and atherothrombotic complications. Inflammatory cells, such as macrophages, T-cells and mast cells, are present in the atherosclerotic tissue and interact with the cells present in the vascular wall. Matrix metalloproteinases (MMPs), a family of more than 20 zinc- and calcium-dependent proteases, are capable of degrading extracellular matrix components. MMPs are involved in both the expansion of atherosclerotic plaques and the weakening of the fibrous cap, thus contributing to the development of vulnerable plaques. Inflammatory cells are suggested to be the major source of MMPs. The aim of this thesis was to evaluate the roles of MMP-3 and MMP-1 in CAD and MI, and how the expression of these MMPs may be modulated by inflammation. This was addressed by genetic analyses of known and novel polymorphisms in the MMP-3 and MMP-1 genes, biochemical analyses of circulating MMP-3, MMP-1, and various cytokines, and angiographic analyses of the extent and severity of CAD. The individual studies were conducted in three different cohorts: i) the Stockholm Coronary Artery Risk Factor (SCARF) study, a case-control study of 387 post-infarction patients and 387 healthy control persons, ii) 164 patients from the Thrombolysis and REOCclusion (TREOC) study, a longitudinal cohort study of patients with ST-elevation MI, and iii) 1177 patients from the Southampton Atherosclerosis Study (SAS) with significant CAD as assessed by coronary angiography. Scrum MMP-3 concentrations were lower in postinfarction patients compared with control subjects. Also, serum concentrations of MMP-3 were lower in the acute stage of MI (within 48 hours) than at the three months follow-up visit. Plasma MMP-1 concentrations did not differ between postinfarction patients and controls. The MMP-3 -1612 5A/6A promoter polymorphism markedly influenced the serum MMP-3 concentrations in two different cohorts of postinfarction patients and in healthy controls. Serum MMP-3 concentrations increased with the number of 6A-alleles. Furthermore, the serum MMP-3 concentration increased with the number of diseased major coronary arteries, as evaluated by coronary angiography. Women had substantially lower serum MMP-3 concentrations compared with men in the SCARF and the TREOC study cohorts. In addition, plasma MMP-1 concentrations were lower in women in the SCARF study. Studies of the MMP-1 gene revealed a haplotype effect of the MMP-1 -519 A/G and -340 C/T promoter polymorphisms on risk of MI. Compared with the A-519 -T-340 haplotype, both the A-519 -C-340 and G-519 -T-340 haplotypes showed a protective effect against MI whereas the G-519-C-340 haplotype was associated with an increased risk of MI. Functional studies of gene expression demonstrated a lower promoter activity of the A-519 -C340 and G-519 -T-340 haplotypes than of the A-519 -T-340 haplotype. Also, mRNA levels in atherosclerotic plaques were significantly lower in plaques retrieved from carriers of the A-519 -C-340 and G-519 -T-340 haplotypes than from carriers of the A-519 -T-340 haplotype. Plasma concentrations of interleukin-2 (IL-2), IL-6, IL-8, and tumour necrosis factor-alpha were higher in postinfarction patients than in controls. Furthermore, there was a difference between MMP-3 and MMP-1 concentrations as regards their respective correlations with several circulating inflammatory cytokines. Correlations were found for MMP-1, but not for MMP-3. In conclusion, the results presented in this thesis reinforce the novel alternative hypothesis of divergent effects of different MMPs in atherosclerosis and CAD. Inflammation is suggested to exert a stronger influence on MMP-1 than on MMP-3. Reduced MMP-3 concentration seems to be associated with MI, whereas increased concentration may promote progression of stable CAD.
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