| 1. |
- Björkman, Inger, 1962-, et al.
(författare)
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Implications of IT in Different Professions
- 2006
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Ingår i: Information Technology: New Generations, 2006. ITNG 2006. Third International Conference on10-12 April 2006. - Las Vegas, Nevada : IEEE Computing Society Press. - 0769524974 ; , s. 11-19
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Development of information systems and IT are continuously ongoing in almost every company and organisation. More and more IT development is performed in organisations characterised by professional work. Two studies are performed to point out two types of professions. One study is carried out at an airbase within the Swedish Air Force and one study is done in a health care organisation in Sweden. The aim of this paper is to describe and analyse the different types of professional work in these organisations. Some implications of the use of IT in different types of professional work are addressed
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| 2. |
- Wilhelmson, Anna S K, et al.
(författare)
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Increased Intimal Hyperplasia After Vascular Injury in Male Androgen Receptor-Deficient Mice
- 2016
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 157:10, s. 3915-3923
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Tidskriftsartikel (refereegranskat)abstract
- Intimal hyperplasia is a vascular pathological process involved in the pathogenesis of atherosclerosis. Data suggest that T, the most important sex steroid hormone in males, protects men from atherosclerotic cardiovascular disease. T mainly acts via the androgen receptor (AR), and in this study we evaluated formation of intimal hyperplasia in male AR knockout (ARKO) mice using a vascular injury model. Two weeks after ligation of the carotid artery, male ARKO mice showed increased intimal area and intimal thickness compared with controls. After endothelial denudation by an in vivo scraping injury, there was no difference in the reendothelialization in ARKO compared with control mice. Ex vivo, we observed increased outgrowth of vascular smooth muscle cells from ARKO compared with control aortic tissue explants; the number of outgrown cells was almost doubled in ARKO. In vitro, stimulation of human aortic vascular smooth muscle cells with a physiological T concentration inhibited both migration and proliferation of the cells. Analyzing the expression of central regulators of cell proliferation and migration, we found that mRNA and protein levels of p27 were lower in uninjured arteries from ARKO mice and that T replacement to castrated male mice increased p27 mRNA in an AR-dependent manner. In conclusion, AR deficiency in male mice increases intimal hyperplasia in response to vascular injury, potentially related to the effects of androgens/AR to inhibit proliferation and migration of smooth muscle cells.
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| 3. |
- Wilhelmson, Anna S K, et al.
(författare)
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Testosterone is an endogenous regulator of BAFF and splenic B cell number
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibro-blastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an alpha-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.
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| 4. |
- Åberg, N David, 1970, et al.
(författare)
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Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats.
- 2009
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Ingår i: The Journal of endocrinology. - 1479-6805. ; 201:1, s. 141-50
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Tidskriftsartikel (refereegranskat)abstract
- IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily s.c. injections of bGH for either 6 or 28 days respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increase the number of BrdU-positive cells. (3)H-thymidine incorporation in vitro revealed that 24 h of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells. This study shows for the first time that 1) peripheral bGH treatment increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.
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| 5. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 6. |
- Hesse, Camilla, et al.
(författare)
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The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
- 2011
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3, s. 494-499
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Tidskriftsartikel (refereegranskat)abstract
- α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
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| 7. |
- Isgaard, Jörgen, 1959, et al.
(författare)
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Cardiovascular activities of ghrelin and synthetic GHS
- 2004
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Ingår i: Ghrelin. - Dordrecht, Netherlands : Kluwer Academic Publisher. - 140207770X ; , s. 113-121
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Recent experimental data demonstrate cardiovascular effects of synthetic growth hormone secretagogues (GHS). These cardiovascular effects include improvement of systolic function in rats after experimental infarction, cardioprotection against postischemic dysfunction in perfused rat hearts and increase of left ventricular ejection fraction in hypopituitaric patients. The proposed natural ligand ghrelin has been isolated and characterized from rat stomach. It was recently reported that a single injection of ghrelin to healthy volunteers decreased blood pressure and increased stroke volume and cardiac output. Similar beneficial cardiovascular effects were observed when ghrelin was administered to patients with chronic heart failure and to rats with experimental myocardial infarction. Specific binding of GHS to rat cardiac membranes and human cardiac tissue has been reported and possible growth hormone (GH) independent effects of GHS have been suggested. We have recently used H9c2 cardiac cells to demonstrate specific and dose-dependent stimulation of thymidine incorporation by GHS and ghrelin. Moreover, binding studies on H9c2 cells demonstrate specific binding of GHS and ghrelin and add further support for an alternative subtype-binding site in the heart compared to the pituitary. In conclusion, accumulating data suggest beneficial effects of GHS and ghrelin on cardiovascular function and these effects may be at least partly independent of GH.
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| 8. |
- Isgaard, Jörgen, 1959, et al.
(författare)
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Ghrelin and GHS on cardiovascular applications/functions.
- 2005
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Ingår i: Journal of endocrinological investigation. - 0391-4097. ; 28:9, s. 838-42
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Tidskriftsartikel (refereegranskat)abstract
- Although initially recognised for their GH-releasing properties, the cardiovascular system has been recognised as a potentially important target for GH secretagogues (GHS). Moreover, a limited number of studies also indicate cardiovascular effects of ghrelin. So far reported cardiovascular effects of GHS and/or ghrelin include lowering of peripheral resistance, possible improvement of contractility and cardioprotective effects both in vivo and in vitro. Taken together, these results offer an interesting perspective on the future where further studies aiming at evaluating a role of GHS and ghrelin in the treatment of cardiovascular disease are warranted.
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| 9. |
- Johansson, Inger, 1962, et al.
(författare)
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Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells.
- 2008
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 149:5, s. 2191-9
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Tidskriftsartikel (refereegranskat)abstract
- Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.
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| 10. |
- Johansson, Inger, 1962
(författare)
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Proliferative and protective effects of the GH/IGF-I axis on cardiomyocytes and neural progenitor cells
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease is the most common cause of mortality in the Western world and the majority of cardiovascular deaths are caused by coronary artery disease or cerebrovascular disease. Growth hormone (GH) is a growth-promoting hormone synthesized by the pituitary. Most of the effects of GH are mediated by local- or liver-produced insulin-like growth factor-I (IGF-I) but GH receptors have been found in a number of extra-hepatic tissues, suggesting direct, IGF-I-independent effects of GH. Synthetic and endogenous GH secretagogues (GHS) release GH from the pituitary and may also exert direct effects in various tissues. Recent data suggest the GH/IGF-I system to improve cardiac performance and to be tissue protective after myocardial infarction. In the brain, the activity of the GH/IGF-I axis has been suggested to improve cognitive function, to exert cell protection after ischemic injury and to stimulate neurogenesis. The aim of this thesis was to investigate direct proliferative and protective effects of compounds of the GH/IGF-I axis on cells or tissue from organs that are exposed to ischemic injury or degenerative disease, such as heart and brain. . Our results suggest that the GH/IGF-I axis is involved in the generation of new cells, both in the heart and in the brain, and that some of these effects are independent of IGF-I. More specifically, the synthetic GHS hexarelin and the endogenous GHS ghrelin were found to have proliferative effects both in rat cardiomyocyte-like cells and in adult rat hippocampal progenitor (AHP) cells in vitro. In addition, hexarelin exerted protective effects in AHP cells after induction of apoptosis. Furthermore, peripheral administration of bovine GH (bGH) to hypophysectomized rats in vivo had proliferative effects in several brain regions and a proliferative effect was also found when AHP cells were incubated with bGH in vitro. The results in this thesis may have potentially important clinical implications in ischemic and degenerative cardiac and cerebral disease, when cell protection and recruitment of new cells are desirable. Keywords: GH, IGF-I, GH secretagogues, ghrelin, cardiovascular, neurogenesis, hippocampus, proliferation, protection
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| 11. |
- Lantero Rodriguez, Marta, et al.
(författare)
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Testosterone reduces metabolic brown fat activity in male mice
- 2021
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 251:1, s. 83-96
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) burns substantial amounts of mainly lipids to produce heat. Some studies indicate that BAT activity and core body temperature are lower in males than females. Here we investigated the role of testosterone and its receptor (the androgen receptor; AR) in metabolic BAT activity in male mice. Castration, which renders mice testosterone deficient, slightly promoted the expression of thermogenic markers in BAT, decreased BAT lipid content, and increased basal lipolysis in isolated brown adipocytes. Further, castration increased the core body temperature. Triglyceride-derived fatty acid uptake, a proxy for metabolic BAT activity in vivo, was strongly increased in BAT from castrated mice ( 4.5-fold increase vs sham-castrated mice) and testosterone replacement reversed the castration-induced increase in metabolic BAT activity. BAT-specific AR deficiency did not mimic the castration effects in vivo and AR agonist treatment did not diminish the activity of cultured brown adipocytes in vitro, suggesting that androgens do not modulate BAT activity via a direct, AR-mediated pathway. In conclusion, testosterone is a negative regulator of metabolic BAT activity in male mice. Our findings provide new insight into the metabolic actions of testosterone.
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| 12. |
- Li, T. T., et al.
(författare)
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Pathogenic antibody response to glucose-6-phosphate isomerase targets a modified epitope uniquely exposed on joint cartilage
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 799-808
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). MethodsIgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. ResultsPeptide GPI(293-307) was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI(293-307) epitopes, and high affinity anti-GPI(293-307) IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI(293-307) IgG antibodies induced arthritis in mice. Moreover, anti-GPI(293-307) IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI(293-307)-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI(293-307) antibodies. ConclusionsWe have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.
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| 13. |
- Svedlund Eriksson, Elin, et al.
(författare)
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Castration of Male Mice Induces Metabolic Remodeling of the Heart
- 2022
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Ingår i: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Androgen deprivation therapy of prostate cancer, which suppresses serum testosterone to castrate levels, is associated with increased risk of heart failure. Here we tested the hypothesis that castration alters cardiac energy substrate uptake, which is tightly coupled to the regulation of cardiac structure and function. Short-term (3-4 weeks) surgical castration of male mice reduced the relative heart weight. While castration did not affect cardiac function in unstressed conditions, we observed reductions in heart rate, stroke volume, cardiac output, and cardiac index during pharmacological stress with dobutamine in castrated vs sham-operated mice. Experiments using radiolabeled lipoproteins and glucose showed that castration shifted energy substrate uptake in the heart from lipids toward glucose, while testosterone replacement had the opposite effect. There was increased expression of fetal genes in the heart of castrated mice, including a strong increase in messenger RNA and protein levels of beta-myosin heavy chain (MHC), the fetal isoform of MHC. In conclusion, castration of male mice induces metabolic remodeling and expression of the fetal gene program in the heart, in association with a reduced cardiac performance during pharmacological stress. These findings may be relevant for the selection of treatment strategies for heart failure in the setting of testosterone deficiency.
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| 14. |
- Westas, Mats, 1972-
(författare)
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Internet-based cognitive behavioural therapy for depression : Effects and experiences among patients with cardiovascular disease
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Depressive symptoms are common in patients with cardiovascular disease (CVD). CVD has a negative impact on patients’ prognosis and health-related quality of life (HRQoL). Guidelines for the treatment of CVD recommend treatment of depressive symptoms. However, the detection rate of depressive symptoms in CVD care is low and patients are therefore at risk of not receiving treatment. The reason for the low detection rate in CVD patients has not been fully explored, but may be related to healthcare professionals or the patients themselves. CVD patients’ experience of how depressive symptoms are discussed or managed by healthcare providers has not currently been fully explored. Today, cognitive behavioural therapy (CBT) is the recommended treatment for mild to moderate depressive symptoms and has been found to be effective in CVD patients. One problem with CBT is the low access to the treatment, which is mainly due to a lack of psychotherapists. A solution could be to use the internet to provide CBT (iCBT), since this has been shown to be effective in the treatment of depressive symptoms in non- CVD populations and is as effective as regular CBT. At the time when this thesis was planned there was a lack of iCBT studies on patients with CVD and depressive symptoms, and more research regarding iCBT in CVD has been called for in the literature. AimThe overall aim of this thesis was to generate knowledge which can lead to improvements in the care of patients with CVD and depressive symptoms. This is done by exploring how depressive symptoms are managed in the healthcare setting from the patient’s perspective, and by evaluating the effects and experiences of an iCBT programme for depressive symptoms in patients with CVD. Design and methodsThis thesis represents two quantitative and two qualitative studies that were performed on the same cohort of participants (n=144) recruited to a randomised controlled trial (RCT) aiming to evaluate a nine-week iCBT programme (n=72) adapted for patients with CVD and depressive symptoms. In the RCT, the comparator was a nine-week online discussion forum (n=72). These participants were recruited via an invitation letter sent to patients diagnosed with CVD (i.e. coronary heart disease, atrial fibrillation/atrial flutter or heart failure) who had contacted four hospitals in southeast Sweden during the past year. Study I had a qualitative study design with an inductive semantic approach. The sample (n=20) was recruited from those who had performed iCBT and had completed at least one module of the treatment programme. The interviews were conducted by telephone using a semi-structured interview guide. Study II was designed as an RCT, and compared the effect of a nine-week iCBT programme adapted for CVD (n=72) with nine weeks of ODF (n=72) on depressive symptoms in CVD patients. Data regarding depressive symptoms and HRQoL was collected at baseline and at nine weeks post-intervention. Study III used the same cohort as study I, and had a qualitative study design with an inductive latent approach. Study IV used a quantitative longitudinal and explorative design. Data regarding depressive symptoms was collected at baseline, at nine weeks post-intervention and at six- and twelve-month follow-ups. ResultsThe mean age of the participants in studies II and IV was 63 years, and 61% (n=89) were men. Atrial fibrillation/flutter was found in 56% (n=81), 44% (n=63) had coronary heart disease and 26% (n=38) had heart failure. The mean age of the participants in studies I and III (n=20) was 62 years, and 55% (n=11) were men. The patients experienced how depressive symptoms were addressed and managed in clinical cardiac care encounters under three main themes: “Not being seen as a whole person”; “Denying depressive symptoms”; and “I was provided with help”. The RCT study showed that iCBT after nine weeks was more effective than ODF in terms of decreasing depressive symptoms and improving HRQoL. At six- and twelve-month follow-ups, the improvements in depressive symptoms in the iCBT group were sustained. At the twelve-month follow-up, it was those who had more depressive symptoms at baseline who also experienced more improvements in depressive symptoms through iCBT, whereas those with heart failure were less likely to improve. The experience of participating in the iCBT programme was perceived as: taking control of the disease; not just a walk in the park; and feeling a personal engagement with the iCBT programme. ConclusionsCVD patients experienced that healthcare professionals focused on somatic symptoms and did not address their depressive symptoms. On the other hand, CVD patients did not always understand that they had depressive symptoms – or denied having depressive symptoms – when meeting healthcare professionals. Those who had received treatment had taken the initiative to address this by themselves or through support from family or friends. A nine-week iCBT programme adapted for CVD and guided by nurses with clinical experience of CVD and psychiatry and a brief education in iCBT seems to be useful for decreasing depressive symptoms and improving HRQoL. The effect of iCBT seems to be more beneficial in CVD patients with higher levels depressive symptoms, whereas the effect of iCBT on heart failure patients is less certain. The iCBT programme adapted to CVD seems to provide knowledge, and was experienced by patients as helpful for taking control of their disease. A CVD-adapted iCBT programme including feedback from nurses with clinical experience of CVD and psychiatry was helpful for engaging with and motivating carrying out the iCBT programme. Participating in the iCBT programme can be demanding and emotionally challenging, but is sometimes necessary to achieve improvements in depressive symptoms.
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| 15. |
- Wilhelmson, Anna S K, et al.
(författare)
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Deficiency of mature B cells does not alter the atherogenic response to castration in male mice
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone deficiency in men is associated with increased atherosclerosis burden and increased cardiovascular risk. In male mice, testosterone deficiency induced by castration increases atherosclerosis as well as mature B cell numbers in spleen. As B cells are potentially pro-atherogenic, we hypothesized that there may be a link between these effects. To address whether mature B cell deficiency alter the atherogenic response to castration, we studied B cell-deficient mu MT and genotype control male mice on an atherosclerosis-prone Apoe(-/-) background that were castrated or sham-operated pre-pubertally and fed a high-fat diet between 8 and 16 weeks of age to accelerate atherosclerosis development. Genotype did not affect the effects of castration on body weight or weights of fat depots and there were no differences in serum cholesterol levels across the four groups. Atherosclerosis assessed by quantification of lesion area in serial sections of the aortic root was significantly increased by castration and by the mu MT mutation, with no significant interaction between genotype and surgery. In conclusion, castration evokes a similar atherogenic response in B cell-deficient mu MT and control mice. These data suggest that atherogenesis following castration is unrelated to the effects of androgens on mature B cell numbers.
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| 16. |
- Wilhelmson, Anna S K, et al.
(författare)
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Testosterone Protects Against Atherosclerosis in Male Mice by Targeting Thymic Epithelial Cells.
- 2018
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 38:7, s. 1519-1527
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Tidskriftsartikel (refereegranskat)abstract
- Androgen deprivation therapy has been associated with increased cardiovascular risk in men. Experimental studies support that testosterone protects against atherosclerosis, but the target cell remains unclear. T cells are important modulators of atherosclerosis, and deficiency of testosterone or its receptor, the AR (androgen receptor), induces a prominent increase in thymus size. Here, we tested the hypothesis that atherosclerosis induced by testosterone deficiency in male mice is T-cell dependent. Further, given the important role of the thymic epithelium for T-cell homeostasis and development, we hypothesized that depletion of the AR in thymic epithelial cells will result in increased atherosclerosis.Prepubertal castration of male atherosclerosis-prone apoE-/- mice increased atherosclerotic lesion area. Depletion of T cells using an anti-CD (cluster of differentiation) 3 antibody abolished castration-induced atherogenesis, demonstrating a role of T cells. Male mice with depletion of the AR specifically in epithelial cells (E-ARKO [epithelial cell-specific AR knockout] mice) showed increased thymus weight, comparable with that of castrated mice. E-ARKO mice on an apoE-/- background displayed significantly increased atherosclerosis and increased infiltration of T cells in the vascular adventitia, supporting a T-cell-driven mechanism. Consistent with a role of the thymus, E-ARKO apoE-/- males subjected to prepubertal thymectomy showed no atherosclerosis phenotype.We show that atherogenesis induced by testosterone/AR deficiency is thymus- and T-cell dependent in male mice and that the thymic epithelial cell is a likely target cell for the antiatherogenic actions of testosterone. These insights may pave the way for new therapeutic strategies for safer endocrine treatment of prostate cancer.
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