| 1. |
- 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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| 2. |
- Bergström, Anders, et al.
(författare)
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Origins and genetic legacy of prehistoric dogs
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 3. |
- Bergström, Göran, 1964, et al.
(författare)
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Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
- 2023
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
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| 4. |
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| 5. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 6. |
- Ekström, Magnus Pär, et al.
(författare)
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The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
- 2019
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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| 7. |
- Malinovschi, Andrei, 1978-, et al.
(författare)
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Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2020
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Ingår i: European Respiratory Journal. - Lausanne, Switzerland : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 56:2
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Tidskriftsartikel (refereegranskat)abstract
- The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (DLCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired DLCO. We examined if the GLI LLN for DLCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, DLCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50–64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for DLCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of DLCO DLCO >GLI LLN but DLCO >GLI LLN but versus 4.5%, p<0.001), chronic airflow limitation (8.5% versus 3.9%, p<0.001) and chronic bronchitis (8.3% versus 4.4%, p<0.01) than subjects (n=13 600) with normal DLCO (>GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for DLCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with DLCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.
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| 8. |
- Nyström, Henrik, 1977, et al.
(författare)
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Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries
- 2006
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Ingår i: Cardiovasc Res. - : Oxford University Press (OUP). - 0008-6363. ; 71:3, s. 557-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function. METHODS: Passive and active properties of conduit vessels were studied using myograph techniques and histological examination. Capillary structure and function was studied using measurements of capillary density in skeletal muscle and by assessing aerobic physical performance in a treadmill setup. Cardiac function was assessed using echocardiography. RESULTS: Myograph experiments revealed an increased diameter and stiffness of the aorta in RetKO. Histological examination showed increased media collagen content and a decreased number of aortic wall layers, however with a similar number of vascular smooth muscle cells. This outward eutrophic remodelling of the aorta was accompanied by endothelial dysfunction. RetKO showed decreased capillary density in skeletal muscle and signs of a defective delivery of capillary oxygen to skeletal muscle, as shown by a decreased physical performance. In RetKO mice, echocardiography revealed an adaptive eccentric cardiac hypertrophy. CONCLUSION: We conclude that retention of PDGF-B during development is essential for a normal conduit vessel function in the adult mouse. Furthermore, PDGF-B retention is also necessary for the development of an adequate capillary density, and thereby for a normal oxygen delivery to skeletal muscle. The lack of primary effects on cardiac function supports the redundant role of PDGF-B in cardiac development.
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| 9. |
- Nyström, Henrik, 1977, et al.
(författare)
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Short-term administration of growth hormone (GH) lowers blood pressure by activating eNOS/nitric oxide (NO)-pathway in male hypophysectomized (Hx) rats
- 2005
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Ingår i: BMC Physiol. - : Springer Science and Business Media LLC. - 1472-6793. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the study was to evaluate the acute and continuous (up to 14 days of treatment) effect of growth hormone (GH) on blood pressure (BP) regulation and to investigate the interplay between GH, nitric oxide (NO) and BP. In un-supplemented and GH supplemented hypophysectomized (Hx) male rats as well as intact rats, continuous resting mean arterial blood pressure (MAP) was measured using telemetry. Baroreceptor activity and the influences of NO on BP control were assessed during telemetric measurement. Furthermore, basal plasma and urine nitrate levels and aortic endothelial nitric oxide synthase (eNOS) expression were analysed. Endothelial function as well as vascular structure in the hindquarter vascular bed was estimated using an in vivo constant-flow preparation. RESULTS: Hypophysectomy was associated with decreased MAP (Hx: 83 +/- 3 vs Intact: 98 +/- 6 mmHg, p < 0.05) and heart rate (HR) (Hx: 291 +/- 4 vs Intact: 351 +/- 7 beat/min, p < 0.05). Endothelial dysfunction and reduced vasculature mass in the hindquarter vascular bed was found in Hx rats. GH substitution caused a further transient decrease in MAP and a transient increase in HR (14% and 16% respectively, p < 0.05). The reduction in MAP appeared to be NO dependent. Aortic eNOS expression was unchanged. GH substitution resulted in an impaired baroreceptor function. Two weeks of GH treatment did not normalise the BP, vascular structure and the endothelial function in the resistance vessels. CONCLUSION: GH substitution seems to have a short lasting effect on lowering blood pressure via activation of the NO-system. An interaction between GH, NO-system and BP regulation can be demonstrated.
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| 10. |
- Oldgren, Jonas, 1964-, et al.
(författare)
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Systematic Coronary Risk Evaluation estimated risk and prevalent subclinical atherosclerosis in coronary and carotid arteries: A population-based cohort analysis from the Swedish Cardiopulmonary Bioimage Study
- 2021
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 28:3, s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- Background It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. Design The design of this study was as a cross-sectional analysis from a population-based study cohort. Methods From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. Results Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score >0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score >0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have >1 carotid plaques (1.67 (1.61-1.74)). Conclusion Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis.
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