| 1. |
- Zetterqvist, Anna, et al.
(författare)
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Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice.
- 2015
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca(2+) signaling have been shown to precede the onset of DR. We recently demonstrated that high extracellular glucose activates the Ca(2+)/calcineurin-dependent transcription factor NFAT in cerebral arteries and aorta, promoting the expression of inflammatory markers. Here we show, using confocal immunofluorescence, that NFAT is expressed in the endothelium of retinal microvessels and is readily activated by high glucose. This was inhibited by the NFAT blocker A-285222 as well as by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. Acute hyperglycemia induced by an IP-GTT (intraperitoneal glucose tolerance test) resulted in increased NFATc3 nuclear accumulation and NFAT-dependent transcriptional activity in retinal vessels of NFAT-luciferase reporter mice. In both Akita (Ins2(+/-) ) and streptozotocin- (STZ-) induced diabetic mice, NFAT transcriptional activity was elevated in retinal vessels. In vivo inhibition of NFAT with A-285222 decreased the expression of OPN and ICAM-1 mRNA in retinal vessels, prevented a diabetes driven downregulation of anti-inflammatory IL-10 in retina, and abrogated the increased vascular permeability observed in diabetic mice. Results identify NFAT signaling as a putative target for treatment of microvascular complications in diabetes.
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| 2. |
- Aggestam, Maria, et al.
(författare)
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How women entrepreneurs build embeddedness : a case study approach
- 2017
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Ingår i: International Journal of Gender and Entrepreneurship. - : Emerald Group Publishing Limited. - 1756-6266 .- 1756-6274. ; 9:3, s. 252-268
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study is to examine how women entrepreneurs are building embeddedness into male-gendered fields and how they are creating embedding in such fields in practice.Design/methodology/approachThe qualitative methodology and three indicative case stories within gastronomic industry are illustrated and analysed.FindingsThe contribution of this study lies in the examination of the multifaceted embedding building process from dis-embedded, marginalised and suppressed position by women entrepreneurs. This was achieved with the help of building embedding through two strategies: sameness, that is, becoming one of the boys and then becoming a challenger, thereby enhancing their professional position.Research limitations/implicationsThe study is subject to limitations; a small sample is not suited for the generalizability of results. The most important implication of this study is the identification of the process of building embeddedness as the most critical resource for women’s entrepreneurship that should be supported by the scholarly and business community.Originality/valueThe theoretical framework developed for this study laid the foundation for developing literature on the embeddedness of women’s entrepreneurship and how the process of creating embedding becomes instrumental in business ownership.
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| 3. |
- Aggestam, Maria, et al.
(författare)
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How women entrepreneurs build embeddedness : a case study approach
- 2017
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Ingår i: International Journal of Gender and Entrepreneurship. - 1756-6266. ; 9:3, s. 252-268
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study is to examine how women entrepreneurs are building embeddedness into male-gendered fields and how they are creating embedding in such fields in practice.Design/methodology/approachThe qualitative methodology and three indicative case stories within gastronomic industry are illustrated and analysed.FindingsThe contribution of this study lies in the examination of the multifaceted embedding building process from dis-embedded, marginalised and suppressed position by women entrepreneurs. This was achieved with the help of building embedding through two strategies: sameness, that is, becoming one of the boys and then becoming a challenger, thereby enhancing their professional position.Research limitations/implicationsThe study is subject to limitations; a small sample is not suited for the generalizability of results. The most important implication of this study is the identification of the process of building embeddedness as the most critical resource for women’s entrepreneurship that should be supported by the scholarly and business community.Originality/valueThe theoretical framework developed for this study laid the foundation for developing literature on the embeddedness of women’s entrepreneurship and how the process of creating embedding becomes instrumental in business ownership.
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| 4. |
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| 5. |
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| 6. |
- Engelbertsen, Daniel, et al.
(författare)
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IL-1R and MyD88 signalling in CD4+ T cells promote Th17 immunity and atherosclerosis
- 2018
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 114:1, s. 180-187
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Tidskriftsartikel (refereegranskat)abstract
- The role of CD4+ T cells in atherosclerosis has been shown to be dependent on cytokine cues that regulate lineage commitment into mature T helper sub-sets. In this study, we tested the roles of IL-1R1 and MyD88 signalling in CD4+ T cells in atherosclerosis. Methods and results We transferred apoe-/-myd88\+/\+ or apoe-/-myd88-/- CD4+ T cells to T-A nd B-cell-deficient rag1-/-apoe-/- mice fed high fat diet. Mice given apoe-/-myd88-/- CD4+ T cells exhibited reduced atherosclerosis compared with mice given apoe-/-myd88\+/\+ CD4+ T cells. CD4+ T cells from apoe-/-myd88-/- produced less IL-17 but similar levels of IFN-c. Treatment of human CD4+ T cells with a MyD88 inhibitor inhibited IL-17 secretion in vitro. Transfer of il1r1-/- CD4+ T cells recapitulated the phenotype seen by transfer of myd88-/- CD4+ T cells with reduced lesion development and a reduction in Th17 and IL-17 production compared with wild type CD4+ T cell recipients. Relative collagen content of lesions was reduced in mice receiving il1r1-/- CD4+ T cells. Conclusion We demonstrate that both IL1R and MyD88 signalling in CD4+ T cells promote Th17 immunity, plaque growth and may regulate plaque collagen levels.
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| 7. |
- Gonçalves, Isabel, et al.
(författare)
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Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes
- 2016
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. Methods: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). Results: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. Conclusions: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.
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| 8. |
- Grönberg, Caitríona, et al.
(författare)
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Recent advances on CD4+ T cells in atherosclerosis and its implications for therapy
- 2017
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 816, s. 58-66
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is an arterial inflammatory disease and the primary cause of cardiovascular disease. T helper (Th) cells are an important part in atherosclerotic plaque as they can be either disease promoting or protective. A body of evidence points to a pro-atherosclerotic role of Th1 cells, whereas the role of Th2, Th17 and iNKT cells seems more complex and dependent on surrounding factors, including the developmental stage of the disease. Opposed to Th1 cells, there is convincing support for an anti-atherogenic role of Tregs. Recent data identify the plasticity of Th cells as an important challenge in understanding the functional role of different Th cell subsets in atherosclerosis. Much of the knowledge of Th cell function in atherosclerosis is based on findings from experimental models and translating this into human disease is challenging. Targeting Th cells and/or their specific cytokines represents an attractive option for future therapy against atherosclerosis, although the benefits and the risk of modulation of Th cells with these novel drug targets must first be carefully assessed.
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| 9. |
- Knutsson, Anki, et al.
(författare)
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Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE-/- mice
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE-/- mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists.
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| 10. |
- Rattik, Sara, et al.
(författare)
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B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice
- 2018
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 111, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of regulatory B (Bregs) and T cells (Tregs). In this study, we aimed to investigate if transfer of B cells pulsed with CTB-p210 can protect against atherosclerosis. Method and results: First, we studied if CTB-p210 can induce Bregs and Tregs in vitro. After pulsing B cells from Apob(tm2gy)ldlr(-/-) or Apoe(-/-) mice with CTB-p210 for 1 h and co-culturing them with naive T cells for 48 h, we observed increased expression of membrane bound TGF beta/latency-associated peptide (mTGF beta/LAP) on B cells and an increased proportion of CD25(hi)FoxP3(+) Tregs. Adoptive transfer of B cells pulsed with CTB-p210 into high-fat diet-fed Apoe(-/-) mice at 8, 10 and 12 weeks of age, reduced the plaque area in the aorta at 20 weeks of age as compared with control-treated (CTB-pOVA treated B cells or PBS) mice. Moreover, mice receiving p210-CTB treated B cells had increased levels of anti-p210 IgG antibodies. Conclusion: Our observations suggest that CTB-p210 pulsed B cells acquire a regulatory phenotype and induce Tregs in vitro. Adoptive transfer of CTB-p210, but not control-treated, B cells into Apoe(-/-) mice decreased atherosclerosis development.
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