| 1. |
- Ebeling Barbier, Charlotte, et al.
(författare)
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Clinically unrecognized myocardial infarction detected at MR imaging may not be associated with atherosclerosis
- 2007
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 245:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To prospectively investigate whether there is support for the hypothesis that clinically unrecognized myocardial infarctions (UMIs) detected at magnetic resonance (MR) imaging have an atherosclerotic pathogenesis similar to that of recognized myocardial infarctions (RMIs). Materials and Methods: After ethics committee approval and informed consent were obtained, gadolinium-enhanced whole-body MR angiography and late-enhancement MR imaging were performed in 248 randomly chosen 70-year-old subjects (123 women, 125 men). Imaging included the aorta and the carotid, renal, and lower limb arteries to the ankle, but not the coronary arteries. Subjects with myocardial infarction (MI) scars at late-enhancement MR imaging were classified as having RMI (n = 11) (those with a diagnosis of MI at the hospital) or UMI (n = 49) (those without a diagnosis of MI at the hospital). The presence of 50% or higher luminal narrowing in any vessel at whole-body MR angiography was considered to represent significant atherosclerosis. Intima-media thickness of the common carotid artery was measured with ultrasonography. C-reactive protein level was measured, and coronary heart disease risk was estimated. Observers were blinded to any previous results. The chi(2) test analysis of variance, and Bonferroni correction were used for statistical analyses. Results: None of the measured parameters differed significantly between the group without MI scars and the UMI group, but parameters were significantly increased in the RMI group (P < .05) compared with those in the group without MI scars. Forty-two of 49 UMIs and nine of 11 RMIs were located within inferolateral segments of the left ventricle. Conclusion: MR imaging-detected UMIs might have a different pathogenesis from that of RMIs or may have the same pathogenesis but may manifest at an earlier stage.
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| 2. |
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| 3. |
- Lejonklou, Margareta Halin, 1966-, et al.
(författare)
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Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring.
- 2017
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 125:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.OBJECTIVES: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.METHODS: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to (BPA0.5; ) or (BPA50; ), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.RESULTS: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels ( compared with , females BPA50 ; compared with , males BPA0.5 ) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls ( number of adipocytes/HPF compared with number of adipocytes/HPF; ) and by 123% in BPA0.5 females compared with BPA50 animals ( number of adipocytes/high power field (HPF) compared with number of adipocytes/HPF; ). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals ( number of adipocytes/HPF compared with number of adipocytes/HPF; ). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.CONCLUSIONS: Developmental exposure to of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at were compared with the offspring of unexposed controls.
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| 4. |
- Lind, Lars, et al.
(författare)
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Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample
- 2014
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 133, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures > 80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p < 0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.
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| 5. |
- Lind, Lars, et al.
(författare)
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Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population
- 2013
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 59, s. 456-461
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Tidskriftsartikel (refereegranskat)abstract
- Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p = 0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p = 0.009) only in subjects with one G-allele (n = 103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p = 0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis. (C) 2013 Elsevier Ltd. All rights reserved.
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| 6. |
- Ng, Esther, et al.
(författare)
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Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample
- 2015
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 140, s. 95-101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level.Objectives: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.Methods: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography-high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model.Results: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7 x 10(-13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8 x 10(-12)) for PCB-118, rs4802104 (p= 1.4 x 10(-9)) for PCB-74 and rs4803413 (p=2.5 x 10(-9)) for PCB-105, all of which map to CYP2B6.Conclusions: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity. (C) 2015 The Authors. Published by Elsevier Inc.
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| 7. |
- Penell, Johanna, et al.
(författare)
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Genetic variation in the CYP2B6 Gene is related to circulating 2,2 ',4,4 '-tetrabromodiphenyl ether (BDE-47) concentrations : an observational population-based study
- 2014
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Ingår i: Environmental Health. - London : BioMed Central (BMC). - 1476-069X. ; 13, s. 34-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Since human CYP2B6 has been identified as the major CYP enzyme involved in the metabolism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and that human 2B6 is a highly polymorphic CYP, with known functional variants, we evaluated if circulating concentrations of a major brominated flame retardant, BDE-47, were related to genetic variation in the CYP2B6 gene in a population sample.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (men and women all aged 70), 25 single nucleotide polymorphisms (SNPs) in the CYP2B6 gene were genotyped. Circulating concentrations of BDE-47 were analyzed by high-resolution gas chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS).Results: Several SNPs in the CYP2B6 gene were associated with circulating concentrations of BDE-47 (P = 10(- 4) to 10(-9)). The investigated SNPs came primarily from two haplotypes, although the correlation between the haplotypes was rather high. Conditional analyses adjusting for the SNP with the strongest association with the exposure (rs2014141) did not provide evidence for independent signals.Conclusion: Circulating concentrations of BDE-47 were related to genetic variation in the CYP2B6 gene in an elderly population.
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| 8. |
- Söderberg, Stefan, et al.
(författare)
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MEASURES OF WAIST AND HIP MODIFY SEX-SPECIFIC ASSOCIATIONS BETWEEN BODY MASS INDEX AND PREVALENCE OF CORONARY ARTERY CALCIFICATION IN OPPOSITE DIRECTIONS
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 13-13
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Obesity is associated with increased risk of cardiovascular disease. However, there is still a debate whether accumulation of fat in certain depots modifies this risk. Using data from the CArdioPulmonary bioImage Study (SCAPIS), we investigated if anthropometric measurements of obesity (waist and hip) modifies the risk of coronary artery calcification. Methods: In the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on coronary artery calcification score (CACS) and anthropometry were recorded and traditional cardiovascular risk factors were measured. Body mass index (BMI) was categorized as; <25, 25-30, 30-35 and >35 kg/m2 , quartiles of waist and hip circumferences were constructed within each BMI category and compared using the lowest quartile as reference. Results were adjusted for site, age, smoking and diabetes status. Results: Obesity (BMI >30 kg/m2 ) was found in 21.9% of men and in 20.5% of women. In both sexes the odds ratio (OR) for CACS >0 increased with increasing BMI categories: comparing <25 and >35 kg/m2 , OR = 2.1 (95% CI: 1.6-2.7) for men and OR = 1.4 (1.2-1.8) for women. In addition, increasing quartiles of waist significantly increased the prevalence of CACS >0 for men [p = 0.05; OR = 1.2 (1.0-1.4) for highest quartile] and women [p = 0.005; OR = 1.3 (1.1-1.5)] while increasing quartiles of hip significantly decreased the prevalence for men [p = 0.005; OR = 0.8 (0.6-0.9)] and women [p = 0.04; OR = 0.8 (0.7-0.9)]. Data on education level and physical activity did not affect the model. Conclusion: Increased BMI is associated with increased prevalence of coronary artery calcification and the distribution of fat modifies this risk. Our results suggest that gluteofemoral adipose tissue (hip) counteracts the negative effects associated with BMI and abdominal adipose tissue (waist).
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| 9. |
- Andersson, J., et al.
(författare)
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Echogenecity of the carotid intima-media complex is related to cardiovascular risk factors, dyslipidemia, oxidative stress and inflammation The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 204:2, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased carotid artery intima-media thickness (IMT), measured by ultrasound, is related to an increased risk of cardiovascular disease. Since presence of echolucent plaques increases the risk further, we investigated if echogenecity of the carotid intima-media complex is related to markers of cardiovascular risk. Our aim was therefore to investigate if intima-media echogenecity is related to cardiovascular risk factors, or to markers of inflammation and oxidation in an exploratory investigation. Methods: The PIVUS cohort study is an observational study of 1016 (509 women and 507 men) randomly chosen individuals aged 70 living in Uppsala, Sweden. Carotid artery ultrasound measurements were performed. IMT and the grey scale median (GSM) value were calculated in the intima-media complex (IM-GSM) in the far wall of the common carotid artery. Traditional risk factors were evaluated together with indices of oxidative stress and inflammation. Results: In the multiple regression analysis, HDL-cholesterol, body mass index, conjugated diens, glutathione, e-selectin and TNF alfa were significantly related to IM-GSM. IMT was independently related to blood pressure, smoking and body mass index. Conclusion: The echolucency of the carotid intima-media was related to several cardiovascular risk factors not related to IMT, such as dyslipidemia, oxidative stress and inflammation. Since the echogenecity of the carotid intima-media complex was related to different risk factors compared to carotid IMT, it is worthwhile to further explore the usefulness of this new marker of the vascular wall. (C) 2009 Published by Elsevier Ireland Ltd.
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| 10. |
- Andersson, J., et al.
(författare)
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The Carotid Artery Plaque Size and Echogenicity are Related to Different Cardiovascular Risk Factors in the Elderly
- 2009
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 44:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- Carotid plaques can be characterised by ultrasound by size and echogenicity. Both size and echogenicity are predictors of cardiovascular events. The aim of this study was to examine whether traditional risk factors and markers of inflammation and oxidation were associated with plaque size and echogenicity. Computerised analysis of carotid plaque size and echogenicity (grey scale median, GSM) were performed by ultrasound in a population-based health survey in 1,016 subjects aged 70 years (PIVUS study). Information on cardiovascular risk factors was collected, together with markers of inflammation and oxidation. Increased Framingham risk score, systolic blood pressure, higher BMI and decreased HDL, lower glutathione levels were related to echolucent plaques. Previous or present smoking was common with significantly more pack-years related to the echorich plaques. Plaque size was associated with increased Framingham risk score, systolic blood pressure, blood glucose levels, smoking, ApoB/A1 ratio, OxLDL, TNF alpha, HOMA insulin resistance, leucocyte count, decreased BCD-LDL and low levels of l-selectin. Low HDL, increased BMI and decreased glutathione levels were associated with the echolucency of carotid plaques, implying metabolic factors to play a role for plaque composition. Markers of inflammation were related to plaque size alone, implying inflammation to be predominantly associated with the amount of atherosclerosis. These results suggest that plaque size and echogenicity are influenced by different risk factors.
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