| 1. |
- 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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| 2. |
- Yao Mattisson, Ingrid, et al.
(författare)
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Immune responses against oxidized LDL as possible targets for prevention of atherosclerosis in systemic lupus erythematosus
- 2021
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE−/− mice). Promoting LDL tolerance through mucosal immunization with an apolipoprotein B-100 peptide p45 (amino acids 661–680) and cholera toxin B-subunit fusion protein increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Treatment with the oxidized LDL-specific antibody Orticumab reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. The present study provides support for oxLDL as a possible target for prevention of cardiovascular complications in SLE. © 2021 The Author(s)
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| 3. |
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| 4. |
- Beser, Jessica, et al.
(författare)
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Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 2021
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- A national point seroprevalence study of SARS-CoV-2 was conducted in Sweden in April–May 2021. In total, 2860 individuals 3 to 90 years old from a probability-based web panel were included. Results showed that an estimated 32.6% of the population in Sweden had detectable levels of antibodies, and among non-vaccinated 20.1% had detectable levels of antibodies. We tested for differences in seroprevalence between age groups and by sex and estimated seroprevalence among previously infected participants by time since reporting.
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| 5. |
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| 6. |
- Choquet, Isabelle, 1965-, et al.
(författare)
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Clogging and lump formation during atmospheric plasma spraying with powder injection downstream the plasma gun
- 2007
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Ingår i: Journal of thermal spray technology (Print). - : Springer Science and Business Media LLC. - 1059-9630 .- 1544-1016. ; 16:4, s. 512-523
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to numerically and experimentally investigate lump formation during atmospheric plasma spraying with powder injection downstream the plasma gun exit. A first set of investigations was focused on the location and orientation of the powder port injector. It turned out impossible to keep the coating quality while avoiding lumps by simply moving the powder injector. A new geometry of the powder port ring holder was designed and optimized to prevent nozzle clogging, and lump formation using a gas screen. This solution was successfully tested for applications with Ni-5wt.%Al and ZrO2-7wt.%Y2O3 powders used in production. The possible secondary effect of plasma jet shrouding by the gas screen, and its consequence on powder particles prior to impact was also studied.
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| 7. |
- 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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| 8. |
- Engelbertsen, Daniel, et al.
(författare)
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T-Helper 2 Immunity Is Associated With Reduced Risk of Myocardial Infarction and Stroke.
- 2013
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Experimental studies in mice have attributed T-helper (Th) 1 and Th2 cells important roles in atherosclerosis, but the clinical importance of these cells in cardiovascular disease (CVD) remains to be clarified. Here, we investigated associations between Th1 and Th2 cells, carotid intima-media thickness, and cardiovascular risk. METHODS AND RESULTS: Blood drawn at baseline and incident cardiovascular events during 15-year follow-up were assessed in 700 participants. Baseline Th1 (CD3(+)CD4(+)interferon-γ(+)) and Th2 (CD3(+)CD4(+)IL-4(+)) cells were analyzed by flow cytometry, and cytokine-release from activated mononuclear leukocytes was measured by multiplex technology. High numbers of Th2 cells were independently associated with decreased mean common carotid intima-media thickness. High numbers of Th2 cells were also independently associated with a reduced risk of acute myocardial infarction in women (hazard ratio, 0.19; 95% confidence interval, 0.06-0.56; P=0.002 for the highest versus the lowest tertile of Th2 cells). Moreover, release of the Th2 cytokine IL-4 from activated mononuclear leukocytes was independently associated with a reduced risk of CVD. No independent associations between Th1 cells and carotid intima-media thickness or CVD risk were found. CONCLUSIONS: Our observations provide the first clinical evidence for a protective role of Th2 immunity in CVD. They also suggest this protection is more prominent in women than in men. In spite of convincing evidence from experimental studies, we found no support for a role of Th1 immunity in CVD.
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| 9. |
- 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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| 10. |
- 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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