| 1. |
- Uhlén, Mathias, et al.
(författare)
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The human secretome
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 2. |
- Nybacka, Sanna, et al.
(författare)
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Carotenoids and alkylresorcinols as objective biomarkers of diet quality when assessing the validity of a web-based food record tool and a food frequency questionnaire in a middle-aged population
- 2016
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Ingår i: BMC Nutrition. - : Springer Science and Business Media LLC. - 2055-0928. ; 2:53
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecently, two web-based dietary assessment tools were developed; a 4-day food record tool (the Riksmaten method), and a food frequency questionnaire (MiniMeal-Q). The aim of this study was to use objective biomarkers to examine the ability of the two methods to capture habitual dietary intake.MethodsIn total, 200 individuals from the pilot study of the Swedish CArdioPulmonary bioImage Study (SCAPIS) participated. Plasma concentration of carotenoids were determined with high-performance liquid chromatography (HPLC) and used as biomarkers of fruit and vegetable intake. A gas chromatography mass spectrometry (GC-MS) method was used to quantify alkylresorcinol homologues, which were used as biomarkers of whole grain wheat and rye intake.ResultsThe correlations between energy-adjusted fruit and vegetable intakes and plasma carotenoid concentrations (except lycopene) were stronger amongst women than men (r = 0.46 and r = 0.20 for the Riksmaten method, and r = 0.50 and r = 0.31 for MiniMeal-Q, respectively). For whole grains, the correlations of energy-adjusted intakes and alkylresorcinols were higher using the Riksmaten method (r = 0.30 and r = 0.29 for women and men) than the MiniMeal-Q (r = 0.25 and r = 0.20, respectively). In regression analyses between plasma carotenoids (except lycopene) and reported intake of fruits and vegetables, the R2 were 21.6 % and 5.1 % for women and men by the Riksmaten method, and correspondingly, 18.0 % and 6.6 % by the MiniMeal-Q. In the final full models, adjusted for smoking and BMI, all regression models remained statistically significant. The regression analyses of plasma alkylresorcinols and reported intake of whole grains showed an R2 of 9.4 % and 9.7 % for women and men by the Riksmaten method, and correspondingly, 5.3 % and 8.4 % by the MiniMeal-Q. In the final full models, adjusted for smoking and age, all regression models remained statistically significant, except for women in MiniMeal-Q.ConclusionBoth dietary assessment methods were able to capture dietary intake based on food groups with a similar precision. Agreements with objective biomarkers ranged from low to moderate, depending on sex and diet quality indicator. While the ability to capture whole grain intake was weak for both methods and sexes, the assessment of vegetable and fruit intake performed in a satisfactory manner for women in both methods.
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| 3. |
- Nybacka, Sanna, et al.
(författare)
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Comparison of a web-based food record tool and a food-frequency questionnaire and objective validation using the doubly labelled water technique in a Swedish middle-aged population
- 2016
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Ingår i: Journal of Nutritional Science. - : Cambridge University Press (CUP). - 2048-6790. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Two web-based dietary assessment tools have been developed for use in large-scale studies: the Riksmaten method ( 4-d food record) and MiniMeal-Q ( food-frequency method). The aim of the present study was to examine the ability of these methods to capture energy intake against objectively measured total energy expenditure ( TEE) with the doubly labelled water technique ( TEEDLW), and to compare reported energy and macronutrient intake. This study was conducted within the pilot study of the Swedish CArdioPulmonary bioImage Study ( SCAPIS), which included 1111 randomly selected men and women aged 50-64 years from the Gothenburg general population. Of these, 200 were enrolled in the SCAPIS diet substudy. TEEDLW was measured in a subsample ( n 40). Compared with TEEDLW, both methods underestimated energy intake: -2.5 ( SD 2.9) MJ with the Riksmaten method; -2.3 ( SD 3.6) MJ with MiniMeal-Q. Mean reporting accuracy was 80 and 82 %, respectively. The correlation between reported energy intake and TEEDLW was r 0.4 for the Riksmaten method ( P < 0.05) and r 0.28 ( non-significant) for MiniMeal-Q. Women reported similar average intake of energy and macronutrients in both methods whereas men reported higher intakes with the Riksmaten method. Energy-adjusted correlations ranged from 0.14 ( polyunsaturated fat) to 0.77 ( alcohol). Bland-Altman plots showed acceptable agreement for energy and energy-adjusted protein and carbohydrate intake, whereas the agreement for fat intake was poorer. According to energy intake data, both methods displayed similar precision on energy intake reporting. However, MiniMeal-Q was less successful in ranking individuals than the Riksmaten method. The development of methods to achieve limited under-reporting is a major challenge for future research.
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| 4. |
- Sayin, Volkan I., et al.
(författare)
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Loss of One Copy of Zfp148 Reduces Lesional Macrophage Proliferation and Atherosclerosis in Mice by Activating p53
- 2014
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Ingår i: Circulation Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7330 .- 1524-4571. ; 115:9, s. 781-791
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Cell proliferation and cell cycle control mechanisms are thought to play central roles in the pathogenesis of atherosclerosis. The transcription factor Zinc finger protein 148 (Zfp148) was shown recently to maintain cell proliferation under oxidative conditions by suppressing p53, a checkpoint protein that arrests proliferation in response to various stressors. It is established that inactivation of p53 accelerates atherosclerosis, but whether increased p53 activation confers protection against the disease remains to be determined. Objective: We aimed to test the hypothesis that Zfp148 deficiency reduces atherosclerosis by unleashing p53 activity. Methods and Results: Mice harboring a gene-trap mutation in the Zfp148 locus (Zfp148(gt/+)) were bred onto the apolipoprotein E (Apoe)(-/-) genetic background and fed a high-fat or chow diet. Loss of 1 copy of Zfp148 markedly reduced atherosclerosis without affecting lipid metabolism. Bone marrow transplantation experiments revealed that the effector cell is of hematopoietic origin. Peritoneal macrophages and atherosclerotic lesions from Zfp148(gt/+)Apoe(-/-) mice showed increased levels of phosphorylated p53 compared with controls, and atherosclerotic lesions contained fewer proliferating macrophages. Zfp148(gt/+) Apoe(-/-) mice were further crossed with p53-null mice (Trp53(-/-) [the gene encoding p53]). There was no difference in atherosclerosis between Zfp148(gt/+) Apoe(-/-) mice and controls on a Trp53(+/-) genetic background, and there was no difference in levels of phosphorylated p53 or cell proliferation. Conclusions: Zfp148 deficiency increases p53 activity and protects against atherosclerosis by causing proliferation arrest of lesional macrophages, suggesting that drugs targeting macrophage proliferation may be useful in the treatment of atherosclerosis.
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| 5. |
- Andersson, Irene, 1978, et al.
(författare)
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Endothelial dysfunction in growth hormone transgenic mice
- 2006
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 110:2, s. 217-25
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Tidskriftsartikel (refereegranskat)abstract
- Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.
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| 6. |
- Andersson, Irene, 1978, et al.
(författare)
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Increased atherosclerotic lesion area in apoE deficient mice overexpressing bovine growth hormone
- 2006
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 188:2, s. 331-40
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Tidskriftsartikel (refereegranskat)abstract
- Human growth hormone (GH) excess is linked to increased cardiovascular morbidity and mortality. However, little is known about the effect of GH excess on atherosclerosis. We developed a new mouse model to assess the hypothesis that GH overexpression accelerates atherosclerotic lesion formation. apoE(-/-) mice were crossed with bovine GH (bGH) transgenic mice to yield apoE(-/-) mice overexpressing bGH (apoE(-/-)/bGH). The mice were fed either standard or Western diet. At 22 weeks, atherosclerotic lesion area of thoracic aorta was larger in apoE(-/-)/bGH mice compared with littermate apoE(-/-) mice fed either diet (standard: +161+/-50%, Western: +430+/-134%). Aortic sinus lesions were more severe in apoE(-/-)/bGH mice fed standard diet compared with littermate apoE(-/-) mice. apoE(-/-)/bGH mice had lower (VLDL+LDL)/HDL ratios compared with littermate apoE(-/-) mice, while systolic blood pressure was higher in apoE(-/-)/bGH mice, irrespective of diet. The levels of serum amyloid A and hepatic CRP mRNA were higher in apoE(-/-)/bGH mice than in littermate apoE(-/-) mice. In conclusion, this study shows that excess GH augments the development of atherosclerosis in apoE(-/-) mice. The mechanisms could be direct effects of GH on cellular processes in the vessel wall or the result of concomitant processes such as hypertension or a general inflammatory state.
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| 7. |
- Björk, Jonas, et al.
(författare)
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Predicting participation in the population-based Swedish cardiopulmonary bio-image study (SCAPIS) using register data
- 2017
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 45, s. 45-49
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To illustrate the importance of access to register data on determinants and predictors of study participation to assess validity of population-based studies. In the present investigation, we use data on sociodemographic conditions and disease history among individuals invited to the Swedish cardiopulmonary bio-image study (SCAPIS) in order to establish a model that predicts study participation. Methods: The pilot study of SCAPIS was conducted within the city of Gothenburg, Sweden, in 2012, with 2243 invited individuals (50% participation rate). An anonymous data set for the total target population (n = 24,502) was made available by register authorities (Statistics Sweden and the National Board of Health and Welfare) and included indicators of invitation to and participation in SCAPIS along with register data on residential area, sociodemographic variables, and disease history. Propensity scores for participation were estimated using logistic regression. Results: Residential area, country of birth, civil status, education, occupational status, and disposable income were all associated with participation in multivariable models. Adding data on disease history only increased overall classification ability marginally. The associations with disease history were diverse with some disease groups negatively associated with participation whereas some others tended to increase participation. Conclusions: The present investigation stresses the importance of a careful consideration of selection effects in population-based studies. Access to detailed register data also for non-participants can in the statistical analysis be used to control for selection bias and enhance generalizability, thereby making the results more relevant for policy decisions.
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| 8. |
- Egecioglu, Emil, 1977, et al.
(författare)
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Growth hormone receptor deficiency in mice results in reduced systolic blood pressure and plasma renin, increased aortic eNOS expression, and altered cardiovascular structure and function
- 2007
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Ingår i: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 292:5, s. E1418-E1425
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Tidskriftsartikel (refereegranskat)abstract
- To study the role of the growth hormone receptor (GHR) in the development of cardiovascular structure and function, female GHR gene-disrupted or knockout (KO) and wild-type (WT) mice at age 18 wk were used. GHR KO mice had lower plasma renin levels (12 ± 2 vs. 20 ± 4 mGU/ml, P < 0.05) and increased aortic endothelial NO synthase (eNOS) expression (146%, P < 0.05) accompanied by a 25% reduction in systolic blood pressure (BP, 110 ± 4 vs. 147 ± 3 mmHg, P < 0.001) compared with WT mice. Aldosterone levels were unchanged, whereas the plasma potassium concentration was elevated by 14% ( P < 0.05) in GHR KO. Relative left ventricular weight was 14% lower in GHR KO mice ( P < 0.05), and cardiac dimensions as analyzed by echocardiography were similarly reduced. Myograph studies revealed a reduced maximum contractile response in the aorta to norepinephrine (NE) and K+ ( P < 0.05), and aorta media thickness was decreased in GHR KO ( P < 0.05). However, contractile force was normal in mesenteric arteries, whereas sensitivity to NE was increased ( P < 0.05). Maximal acetylcholine-mediated dilatation was similar in WT and GHR KO mice, whereas the aorta of GHR KO mice showed an increased sensitivity to acetylcholine ( P < 0.05). In conclusion, loss of GHR leads to low BP and decreased levels of renin in plasma as well as increase in aortic eNOS expression. Furthermore, GHR deficiency causes functional and morphological changes in both heart and vasculature that are beyond the observed alterations in body size. These data suggest an important role for an intact GH/IGF-I axis in the maintenance of a normal cardiovascular system.
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| 9. |
- Egecioglu, Emil, 1977, et al.
(författare)
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Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice.
- 2006
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 290:2, s. E317-25
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that growth hormone (GH) overexpression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AgRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR-/- and littermate control (+/+) mice to determine whether ghrelin's acute effects on appetite are dependent on GHR signaling. GHR-/- mice were also analyzed with respect to serum levels of lipoproteins, apolipoprotein (apo)B, leptin, glucose, and insulin as well as body composition. Central injection of ghrelin into the third dorsal ventricle increased food consumption in +/+ mice, whereas no change was observed in GHR-/- mice. After ghrelin injection, AgRP mRNA expression in the hypothalamus was higher in +/+ littermates than in GHR-/- mice, indicating a possible importance of AgRP in the GHR-mediated effect of ghrelin. Compared with controls, GHR-/- mice had increased food intake, leptin levels, and total and intra-abdominal fat mass per body weight and deceased lean mass. Moreover, serum levels of triglycerides, LDL and HDL cholesterol, and apoB, as well as glucose and insulin levels were lower in the GHR-/- mice. In summary, ghrelin's acute central action to increase food intake requires functionally intact GHR signaling. Long-term GHR deficiency in mice is associated with high plasma leptin levels, obesity, and increased food intake but a marked decrease in all lipoprotein fractions.
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| 10. |
- Ekstrand, Matias, et al.
(författare)
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Depletion of ATP and glucose in advanced human atherosclerotic plaques
- 2017
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Ingår i: PLoS One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Severe hypoxia develops close to the necrotic core of advanced human atherosclerotic plaques, but the energy metabolic consequences of this hypoxia are not known. In animal models, plaque hypoxia is also associated with depletion of glucose and ATP. ATP depletion may impair healing of plaques and promote necrotic core expansion. To investigate if ATP depletion is present in human plaques, we analyzed the distribution of energy metabolites (ATP, glucose, glycogen and lactate) in intermediate and advanced human plaques.Snap frozen carotid endarterectomies from 6 symptomatic patients were analyzed. Each endarterectomy included a large plaque ranging from the common carotid artery (CCA) to the internal carotid artery (ICA). ATP, glucose, and glycogen concentrations were lower in advanced (ICA) compared to intermediate plaques (CCA), whereas lactate concentrations were higher. The lowest concentrations of ATP, glucose and glycogen were detected in the perinecrotic zone of advanced plaques.Our study demonstrates severe ATP depletion and glucose deficiency in the perinecrotic zone of human advanced atherosclerotic plaques. ATP depletion may impair healing of plaques and promote disease progression.
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