| 1. |
- Magnusson, Björn, 1976, et al.
(författare)
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Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.
- 2008
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Ingår i: Metabolism: clinical and experimental. - : Elsevier BV. - 1532-8600. ; 57:9, s. 1307-13
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Tidskriftsartikel (refereegranskat)abstract
- Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet. By analysis of CIDEC expression in 65 human tissues, we conclude that human CIDEC is predominantly expressed in subcutaneous adipocytes. Together, these observations led us to investigate the effect of decreased CIDEC expression in cultured 3T3-L1 adipocytes. Small interfering RNA-mediated knockdown of CIDEC resulted in an increased basal release of nonesterified fatty acids, decreased responsiveness to adrenergic stimulation of lipolysis, and increased oxidation of endogenous fatty acids. Thus, we suggest that CIDEC is a regulator of adipocyte lipid metabolism and may be important for the adipocyte to adapt to changes in energy availability.
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| 2. |
- Behre, Carl Johan, 1968, et al.
(författare)
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Dissociation between adipose tissue expression and serum levels of adiponectin during and after diet-induced weight loss in obese subjects with and without the metabolic syndrome
- 2007
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Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 56:8, s. 1022-8
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to examine if dysmetabolic subjects (MetS+) have lower adiponectin gene expression and lower circulating adiponectin levels than non-dysmetabolic obese subjects (MetS-) at baseline, if adiponectin expression and adiponectin concentration rise more in the dysmetabolic group during weight loss, and if v-SNARE Vti1a (vesicle transport soluble NSF attachment protein receptor vps10p tail interacting 1a) expression increases during the weight loss, as a mechanism for increased adiponectin secretion. Twenty-one obese MetS+ and 19 obese MetS- subjects underwent a very low-energy diet for 16 weeks followed by 2 weeks of refeeding. Abdominal subcutaneous adipose tissue biopsies and blood samples were taken before, during, and after dieting for DNA microarray, reverse transcriptase-polymerase chain reaction, and biochemical analyses. Serum adiponectin was also assessed in a sex- and age-matched healthy, nonobese reference group. Weight decreased by 26.3+/-9.8 kg in the MetS+ group and 28.2+/-8.4 kg in the MetS- group with concomitant reductions in insulin, hemoglobin A1c, and triglycerides that were more pronounced in the MetS+ group. Initially, the MetS+ subjects had lower serum adiponectin, but the differences disappeared at week 8, with a continuous increase in serum adiponectin throughout the study in both groups to a level that was higher than in the reference group. The expression of adiponectin and v-SNARE Vti1a did not differ between the groups or over time. In conclusion, obese subjects with the metabolic syndrome had lower circulating adiponectin than subjects without the syndrome. Weight loss increased serum levels of adiponectin without a parallel increase in adiponectin gene expression. The mechanisms involved in the regulation of adiponectin levels merits further investigation.
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| 3. |
- Ekman, Inger, 1952, et al.
(författare)
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Can treatment with ACE-inhibitors in elderly patients with moderate to severe heart failure be improved by a nurse-monitored structured care program?
- 2003
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Ingår i: Heart & Lung. - 0147-9563. ; 32:1, s. 3-9
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Tidskriftsartikel (refereegranskat)abstract
- Can treatment with angiotensin-converting enzyme inhibitors in elderly patients with moderate to severe chronic heart failure be improved by a nurse-monitored structured care program? A randomized controlled trial. OBJECTIVE: The purpose of this study was to examine whether a nurse-monitored structured care program resulted in a more effective use of angiotensin-converting enzyme (ACE) inhibitors in elderly patients compared with standard care in patients with chronic heart failure (CHF). METHODS: Hospitalized patients were screened to identify individuals with CHF, age more than 65 years, New York Heart Association classification III to IV, and no contraindications to ACE inhibitor treatment. One hundred forty-five patients were randomized to a nurse-monitored structured care program that included uptitration of enalapril to a target dose of 10 mg twice a day or to standard care. Six-month follow-up data were collected. RESULTS: The mean age of the randomized patients was 81 years. Although the proportion of patients treated with an ACE inhibitor did not differ between structured care (70%) and standard care (64%), the number of patients with the target ACE inhibitor dose was significantly higher in the structured care group (26% versus 11% in the standard care group; P <.018). Treatment had to be discontinued in 26% of the patients because of adverse effects. CONCLUSION: The patients in this study were older than in previous intervention studies and had considerable comorbidity and reduced tolerance for ACE inhibitors. ACE inhibitor treatment was underused but improved with the structured care program, although achieved treatment levels were below those in the large intervention trials in patients with CHF.
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| 4. |
- Englund, Katarina, et al.
(författare)
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Beslutsstöd gav bättre diagnostik och vård av barn med fetma. : Decision support system improved the care of children and adolescents with obesity
- 2013
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Ingår i: Läkartidningen. - 0023-7205. ; 110:23-24, s. 1165-7
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Tidskriftsartikel (refereegranskat)abstract
- Ett webbaserat beslutsstöd för hälsofrämjande, förebyggande och behandlande insatser mot fetma bland barn och vuxna har utvecklats i Västra Götalandsregionen. Eventuella förändringar i omhändertagandet vid barn- och ungdomsmedicinska mottagningar av detta utvärderades. Vid samtliga mottagningar vägdes och mättes barn i större utsträckning 2011 än 2005, och fetmadiagnosen baserades oftast på BMI-uträkning. Andelen barn och ungdomar som fått diagnosen fetma mer än fördubblades under perioden 2005–2011. Fler barnmottagningar och fler yrkesgrupper deltog 2011 i vården av barn med fetma. Trots det var det fortfarande en majoritet av barnen och ungdomarna med fetma som inte uppmärksammades av hälso- och sjukvården.
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| 5. |
- Gummesson, Anders, 1973, et al.
(författare)
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Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women.
- 2011
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381.
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Tidskriftsartikel (refereegranskat)abstract
- Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
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| 6. |
- Gummesson, Anders, 1973, et al.
(författare)
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Relations of Adipose Tissue Cell Death-Inducing DFFA-like Effector A Gene Expression to Basal Metabolic Rate, Energy Restriction and Obesity: Population-based and Dietary Intervention Studies.
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4759-65
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Tidskriftsartikel (refereegranskat)abstract
- Context: Cell death-inducing DFFA-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. Objective: To investigate the putative link between CIDEA and basal metabolic rate in humans, and to further elucidate the role of CIDEA in human obesity. Design: We have explored CIDEA gene expression in adipose tissue in two different human studies: A cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n=92), and a longitudinal intervention-study of obese subjects treated with a very low calorie diet (VLCD study, n=24). Results: The CIDEA gene was predominantly expressed in adipocytes as compared to other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age and gender (p=0.014). VLCD induced an increase in adipose tissue CIDEA expression (p<0.0001) with a subsequent decrease in response to refeeding (p<0.0001). Reduced CIDEA gene expression was associated with a high body fat content (p<0.0001) and with high insulin levels (p<0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with BMI-matched controls. In a separate sample of VLCD-treated subjects (n=10), uncoupling protein 1 expression was reduced during diet (p=0.0026) and inversely associated with CIDEA expression (p=0.0014). Conclusion: The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
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| 7. |
- Hägg, Daniel, 1974, et al.
(författare)
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Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes.
- 2008
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Ingår i: International journal of molecular medicine. - 1107-3756. ; 21:6, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.
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| 8. |
- Sachdev, P. S., et al.
(författare)
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STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
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| 9. |
- 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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| 10. |
- 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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| 11. |
- Zethelius, Björn, 1962-
(författare)
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Proinsulin and Insulin Sensitivity as Predictors of Type 2 Diabetes Mellitus and Coronary Heart Disease : Clinical Epidemiological Studies with up to 27 Years of Follow-Up
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Defects in insulin secretion and insulin action are the major abnormalities in the development of Type 2 diabetes. Hyperinsulinemia is a risk marker for Type 2 diabetes and according to some, but not in all studies also for coronary heart disease (CHD). Conventional insulin assays measure immunoreactive insulin including proinsulin-like molecules. Proinsulin and insulin measured by specific methods, insulin sensitivity measured by the euglycemic insulin clamp and early insulin response after a glucose challenge give more detailed information and may be better estimates of true risk for Type 2 diabetes and CHD. This study examined relationships between proinsulin, insulin, insulin secretion and insulin sensitivity for the development of Type 2 diabetes and CHD. The investigation of the prognostic significance of proinsulin and insulin for the development of Type 2 diabetes and CHD was performed in prospective studies of 50-year and 70-year-old men in a population-based cohort. The results indicated, that increased proinsulin concentrations, was a marker of increased risk for Type 2 diabetes independent of measurements of insulin secretion and insulin sensitivity whereas insulin was not. Proinsulin was shown to be a predictor for CHD mortality and morbidity, respectively, independent of conventional risk factors, whereas insulin was not. Insulin sensitivity measured by the gold standard euglycemic insulin clamp at age 70 was a predictor of CHD morbidity, independently of established risk factors.In summary, these data provide evidence that an increased concentration of proinsulin and not an elevated plasma insulin level per se, that constitutes the association with Type 2 diabetes and CHD and that insulin resistance per se, is associated with CHD risk.
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| 12. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 13. |
- Agewall, S, et al.
(författare)
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Insulin sensitivity and hemostatic factors in clinically healthy 58-year-old men.
- 2000
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 84:4, s. 571-5
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this cross-sectional study was to investigate the relationship between factors of the coagulation- and fibrinolysis systems and insulin sensitivity in 104 clinically healthy, 58-years-old men. Insulin sensitivity (hyperinsulinemic euglycemic clamp) adjusted for lean body mass, the metabolic syndrome according to a suggested definition, and different factors in the coagulation- and fibrinolysis system were determined. Subjects with the metabolic syndrome were characterised by increases in PAI-1 activity, tPA antigen, protein C and protein S and low concentrations of tPA activity. Insulin sensitivity was independently and reversibly associated with PAI-1 (p = 0.014) and directly with tPA activity (p = 0.001). Insulin sensitivity was also significantly negatively associated with protein S and protein C and several components in the metabolic syndrome, however not remaining significant in multivariate analyses. Protein C and protein S were significantly associated with PAI-1 activity, tPA activity (negatively), tPA antigen and antithrombin III. In conclusion, the data indicated that insulin resistance and several of the clustering components in the metabolic syndrome are accompanied by increased plasma concentrations of the anticoagulatory proteins C and S which may represent a mechanism which counteracts the concomitantly occurring hypofibrinolysis.
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| 14. |
- Agewall, S, et al.
(författare)
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Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up
- 2001
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 249:1, s. 305-314
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objective was to analyse whether a favourable change in risk factors, caused by a comprehensive risk factor modification programme, affected intima-media thickness (IMT) in the common carotid artery, and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years (at randomization) and one or more of the following: Serum cholesterol level > 6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed antihypertensive treatment since many years. In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline, 119 were re-examined after 3.3 years, and 97 patients were available for examination after mean follow-up time of 6.2 years. Cardiovascular events were available for all randomized patients. INTERVENTIONS: The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses. The diet recommendations were similar to established guidelines. Overweight patients were instructed to lose weight, and diabetic patients were systematically taught self-monitoring of blood glucose. Smokers were invited to a smoking cessation programme with five weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved. Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common carotid artery as measured by ultrasound. Cardiovascular events during follow-up. RESULTS: Significant net reductions were seen for serum cholesterol, triglycerides, fasting glucose and smoking. No difference in change in IMT was observed during follow-up between the two randomization groups. The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status, and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group. Total mortality was lower in the intervention group, compared with the usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk populations, long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed, had they been re-examined. Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme. The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline.
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| 15. |
- Andersson, Eva M., 1968, et al.
(författare)
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Partial Mediation by Cadmium Exposure of the Association Between Tobacco Smoking and Atherosclerotic Plaques in the Carotid Artery
- 2018
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 187:4, s. 806-816
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to cadmium confers increased cardiovascular risk. Tobacco smoke contains cadmium, which, hypothetically, may mediate parts of the tobacco-associated risk of developing atherosclerotic plaques. Baseline data from the Swedish Malmo Diet and Cancer cohort (1991-1996) were used to test this hypothesis. Mediation analysis was used to examine associations between smoking and blood cadmium levels and the prevalence of ultrasound-assessed carotid atherosclerotic plaques. The total association with smoking status (never smokers, 2 categories of former smokers, and current smokers) was split into direct and indirect association, and the proportion mediated was estimated. The adjusted estimated plaque prevalence was approximately 27% among never smokers. We identified both a direct and an indirect pathway between smoking and carotid plaques; the indirect association, through cadmium, was observed among current smokers and former smokers who had quit smoking less than 15 years before. For current smokers, the prevalence ratio for plaque was 1.5, with 60%-65% of the association with smoking being mediated through cadmium. Recent former smokers had a prevalence ratio of 1.3, and 40%-45% was mediated through cadmium. Long-time former smokers had a prevalence ratio of 1.2, but none of the association was mediated through cadmium. In conclusion, about two-thirds of the proatherosclerotic association with smoking was mediated by cadmium.
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| 16. |
- Andersson, Sandra, et al.
(författare)
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The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115911-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.
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| 17. |
- Angelhed, Jan-Erik, 1948, et al.
(författare)
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Measurement of Lower-Leg Volume Change by Quantitative Computed Tomography
- 2008
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 49:9, s. 1024-1030
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lower-leg edema is a common symptom in many diseases. A precise method with low variability for measurement of edema is warranted in order to obtain optimal conditions for investigation of treatment effects. Purpose: To evaluate computed tomography for precise measurement of lower-leg muscle and adipose tissue volumes using a very low level of effective radiation dose. Material and Methods: Eleven volunteers were examined three times during 1 day, either as two consecutive examinations in the morning and one single examination in the afternoon, or as one examination in the morning and two in the afternoon. Eleven scans with computed tomography were made at each examination, and lower-leg volumes were calculated from automatically measured scan areas and interscan distances. Volumes for muscle, adipose tissue, and bone were calculated separately. Minimal radiation dose was used. Results: Mean difference between the repeated examinations was −0.1 ml for total volume, −1.4 ml for muscle, and 1.6 ml for adipose tissue volume. The corresponding 95% confidence intervals were −6.5 to 6.0 ml, −3.5 to 6.5 ml, and −7.0 to 4.0 ml, respectively. The resulting effective dose was 0.5 µSv to one leg. Conclusion: Computed tomography can be used as a precise quantitative method to measure small volume changes of the lower leg as a whole, and separately for muscle and adipose tissue. The results were obtained with a negligible effective dose, lower than that delivered by modern fan-beam dual-energy X-ray absorptiometry whole-body examinations and equal to a few hours of background radiation.
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| 18. |
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| 19. |
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| 20. |
- Asplund, Annika, 1979, et al.
(författare)
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Hypoxic regulation of secreted proteoglycans in macrophages.
- 2010
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 20:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages are prominent in hypoxic areas of atherosclerotic lesions, and their secreted proteoglycans (PG), such as versican, can modulate the retention of lipoproteins and the activity of enzymes, cytokines, and growth factors involved in atherogenesis. In this study, we report the effects of hypoxia on PG secreted by human monocyte-derived macrophages (HMDM) and the potential regulation by the transcription factor hypoxia-inducible factor (HIF-1alpha and HIF-2alpha). We found that versican co-localized with HIF-1alpha in macrophage-rich areas in human advanced atherosclerotic lesions. Versican and perlecan mRNA expression increased after exposure to 0.5% O(2) (hypoxia) compared with 21% O(2) (control cells). Using precursors to GAG biosynthesis combined with immunoabsorption with a versican antibody an increased versican synthesis was detected at hypoxia. Furthermore, siRNA knockdown of HIF-1alpha and HIF-2alpha in THP-1 cells showed that the hypoxic induction of versican and perlecan mRNA expression involved HIF signaling. Versican expression was co-regulated by HIF-1alpha and HIF-2alpha but expression of perlecan was influenced only by HIF-1alpha and not by HIF-2alpha knockdown. The results show that oxygen concentration is an important modulator of PG expression in macrophages. This may be a novel component of the complex role of macrophages in atherosclerosis.
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| 21. |
- Azzouz, Mehjar, 1999, et al.
(författare)
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Air pollution and biomarkers of cardiovascular disease and inflammation in the Malmo Diet and Cancer cohort
- 2022
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Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Air pollution is associated with increased risk of cardiovascular disease, possibly through chronic systemic inflammation that promotes the progression of atherosclerosis and the risk of cardiovascular events. This study aimed to investigate the associations between air pollution and established biomarkers of inflammation and cardiovascular disease. Methods The Cardiovascular Subcohort of the Malmo Diet and Cancer cohort includes 6103 participants from the general population of Malmo, Sweden. The participants were recruited 1991-1994. Annual mean residential exposure to particulate matter < 2.5 and < 10 mu m (PM2.5 and PM10), and nitrogen oxides (NOx) at year of recruitment were assigned from dispersion models. Blood samples collected at recruitment, including blood cell counts, and biomarkers (lymphocyte- and neutrophil counts, C-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), ceruloplasmin, orosomucoid, haptoglobin, complement-C3, and alpha-1-antitrypsin) were analyzed. Multiple linear regression models were used to investigate the cross-sectional associations between air pollutants and biomarkers. Results The mean annual exposure levels in the cohort were only slightly or moderately above the new WHO guidelines of 5 mu g/m(3) PM2.5 (10.5 mu g/m(3) PM2.5). Residential PM2.5 exposure was associated with increased levels of ceruloplasmin, orosomucoid, C3, alpha-1-antitrypsin, haptoglobin, Lp-PLA(2) and the neutrophil-lymphocyte ratio. Ceruloplasmin, orosomucoid, C3 and alpha-1-antitrypsin were also positively associated with PM10. There were no associations between air pollutants and suPAR, leukocyte counts or CRP. The associations between particles and biomarkers were still significant after removing outliers and adjustment for CRP levels. The associations were more prominent in smokers. Conclusion Long-term residential exposure to moderate levels of particulate air pollution was associated with several biomarkers of inflammation and cardiovascular disease. This supports inflammation as a mechanism behind the association between air pollution and cardiovascular disease.
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| 22. |
- Barregård, Lars, 1948, et al.
(författare)
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Blood Cadmium Levels and Incident Cardiovascular Events during Follow-up in a Population-Based Cohort of Swedish Adults: The Malmo Diet and Cancer Study
- 2016
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:5, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cadmium exposure may increase the risk of cardiovascular disease. The only published longitudinal study on cadmium and incident cardiovascular disease was performed in American Indians with relatively high cadmium exposure. OBJECTIVES: Our aim was to examine the association between blood cadmium at baseline and incident cardiovascular events in a population-based study of Swedish men and women with cadmium levels similar to those of most European and U.S. populations. METHODS: A Swedish population-based cohort (n = 6,103, age 46-67 years) was recruited between 1991 and 1994. After we excluded those with missing data on smoking, 4,819 participants remained. Acute coronary events, other major cardiac events, stroke, and cardiovascular mortality were followed until 2010. Associations with blood cadmium (estimated from cadmium in erythrocytes) were analyzed using Cox proportional hazards regression including potential confounders and important cardiovascular risk factors. RESULTS: Hazard ratios for all cardiovascular end points were consistently increased for participants in the 4th blood cadmium quartile (median, 0.99 mu g/L). In models that also included sex, smoking, waist circumference, education, physical activity, alcohol intake, serum triglycerides, HbA1c, and C-reactive protein, the hazard ratios comparing the highest and lowest quartiles of exposure were 1.8 (95%CI: 1.2, 2.7) for acute coronary events, and 1.9 (1.3, 2.9) for stroke. Hazard ratios in never-smokers were consistent with these estimates. CONCLUSIONS: Blood cadmium in the highest quartile was associated with incident cardiovascular disease and mortality in our population-based samples of Swedish adults. The consistent results among never-smokers are important because smoking is a strong confounder. Our findings suggest that measures to reduce cadmium exposures are warranted, even in populations without unusual sources of exposure.
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| 23. |
- Barregård, Lars, 1948, et al.
(författare)
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Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults
- 2021
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Ingår i: Environmental health perspectives. - 1552-9924 .- 0091-6765. ; 129:6
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Tidskriftsartikel (refereegranskat)abstract
- The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined.Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study.Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history.The median B-Cd concentration was 0.24 μ g / L . The prevalence of positive coronary artery calcium ( CACS > 0 ) was 41% and the prevalence of CACS ≥ 100 was 13%. Relative to the lowest quartile (Q) of B-Cd ( < 0.16 μ g / L ), the highest quartile (median 0.63 μ g / L ) was associated with a small but significant increase in CACS > 0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS ≥ 100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS > 0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS ≥ 100 (17 cases in Q4).Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.
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| 24. |
- Barregård, Lars, 1948, et al.
(författare)
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Cadmium exposure in relation to insulin production, insulin sensitivity and type 2 diabetes: A cross-sectional and prospective study in women
- 2013
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351. ; 121, s. 104-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cadmium is a wide-spread pollutant. Observational studies suggest associations Objectives: To examine whether cadmium exposure is associated with impaired glucose tolerance and Methods: Oral glucose tolerance tests were used in a screening examination of 64-year old women Results: At baseline, neither blood nor urinary cadmium concentrations showed any statistically Conclusions: This is the first study of cadmium and diabetes with detailed data on pancreatic beta-cell
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| 25. |
- Barregård, Lars, 1948, et al.
(författare)
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Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women
- 2014
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351. ; 135, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 mu g/L (median 0.34 mu g/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 mu g/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1-3 in women with DM (OR 4.2, 95% confidence interval 1.1-12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT regarding effect of B-Cd on eGFR or RBP. Conclusion: The present study provides support for the hypothesis that women with DM have higher risk of renal glomerular damage from cadmium exposure compared to women without DM. (C) 2014 Elsevier Inc. All rights reserved.
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