| 1. |
- Bernberg, Evelina, 1981, et al.
(författare)
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Effects of social isolation and environmental enrichment on atherosclerosis in ApoE-/- mice
- 2008
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Ingår i: Stress. - 1607-8888 .- 1025-3890. ; 11:5, s. 381-9
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Tidskriftsartikel (refereegranskat)abstract
- Social support and a stimulating environment have been suggested to reduce stress reactions and cardiovascular risk. The aim of this study was to assess the role of environmental enrichment and social interaction for development of atherosclerosis in atherosclerosis prone mice. Male ApoE-/- mice were divided into four groups and followed during 20 weeks: (i) enriched environment (E, n=12), (ii) deprived environment (ED, n=12), (iii) enriched environment with exercise (E-Ex, n=12) and (iv) socially deprived by individual housing (SD, n=10). Plasma lipid and cytokine concentrations were measured. Atherosclerosis was quantified in cross-sections of innominate artery and en face in thoracic aorta. Plaque area was significantly increased in SD mice in the innominate artery (P<0.05 vs. all other groups), but not in the thoracic aorta. Plasma lipids were increased in SD mice (P<0.001 vs. all for total cholesterol, P<0.05 vs. E and P<0.01 vs. ED for triglycerides). Plasma concentration of granulocyte-colony stimulating factor (G-CSF) was decreased in SD mice compared to E mice (P<0.05). Thus, social isolation increased atherosclerosis and plasma lipids in ApoE-/- mice. Reduction in plasma G-CSF levels may hamper endothelial regeneration in the atherosclerotic process. While environmental enrichment did not affect atherosclerosis, social isolation accelerated atherosclerosis.
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| 2. |
- Bernberg, Evelina, 1981, et al.
(författare)
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Repeated exposure to stressors do not accelerate atherosclerosis in ApoE-/- mice
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 204:1, s. 90-95
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Tidskriftsartikel (refereegranskat)abstract
- Psychosocial stress is suggested to play a significant role in development of cardiovascular disease. To evaluate the effects of repeated exposure to stress on atherosclerosis in atherosclerosis-prone ApoE(-/-) mice we used five different stressors. We further sought to determine whether stress combined with high salt diet induces dysfunctional neurohormonal regulation and impaired salt excretion, thus amplifying the atherogenic potential of salt. The five stressors were evaluated in male C57BL/6 mice and ApoE(-/-) mice (studies I and II) and then used in female ApoE(-/-) mice to study their effect on atherosclerosis (study III). The mice in study III received standard or high salt diet (8%) alone or in combination with stress for 12 weeks. Urine and plasma were collected for corticosterone and lipid analysis, respectively. Acute blood pressure (BP) and heart rate (HR) responses to stress were measured using telemetry. Plaque burden was assessed in the thoracic aorta and aortic root. Plaque morphology was investigated regarding macrophages and collagen content. Urinary corticosterone chronically increased in stressed mice (P<0.05 control vs. stress, P<0.05 control salt vs. stress salt). BP and HR increased acutely during all stressors (P<0.05). Body weight gain decreased significantly in the stress group (P<0.05 vs. control). However, stress did not alter plasma lipid levels, plaque area or plaque morphology. Increased BP and HR suggest an acute stress-related response in ApoE(-/-) mice. Furthermore, stress chronically decreased body weight gain and increased urinary corticosterone levels. Notably, despite an apparent stress effect, stress affected neither atherogenesis nor plaque morphology.
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| 3. |
- Bernberg, Evelina, 1981, et al.
(författare)
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Social disruption stress increases IL-6 levels and accelerates atherosclerosis in ApoE-/- mice.
- 2012
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 221:2, s. 359-65
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that different forms of stress have distinctive effects on atherogenesis in mice. We showed that social stress increase atherosclerosis in ApoE(-/-) mice, while more physical forms of stress do not. Here we evaluated the effect of social disruption (SDR) stress on atherogenesis and evaluated cytokine release after SDR-stress and five more physical stressors.
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| 4. |
- Bernberg, Evelina, 1981
(författare)
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The effects of stress on atherosclerosis in mice
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psychosocial stress has been recognized as an independent risk factor for cardiovascular disease and atherosclerosis. However, little is known about the mechanisms converting this psychosocial load into physical disease. This thesis aims to find and evaluate a well controlled animal model for stress and use it to study the long term consequences of stress on atherosclerosis. We also aim to use this model to search for mechanisms causing stress to accelerate the progression of atherosclerosis. We exposed atherosclerosis-prone ApoE-/- mice to social isolation, five physical stressors or social disruption stress (SDR-stress). A subgroup of SDR-mice and unstressed mice were treated with metoprolol. Atherosclerosis was assessed and blood samples were collected for analysis of corticosterone, lipids and cytokines. We found that social isolation and SDR-stress increased atherosclerosis, while the five more physical stressors failed to be atherogenic. Metoprolol per se reduced atherosclerosis in unstressed mice. Plasma corticosterone levels were increased after all 5 physical stressors and SDR-stress, but not in socially isolated mice. Plasma lipid levels were increased in socially isolated mice. Serum levels of the haemotopoietic cytokine G-CSF were decreased in socially isolated mice, pro-inflammatory cytokines IL-6 and CXCL1 were increased after SDR-stress, but no effects on cytokine release was found after the five physical stressors. β-blockade with metoprolol likely reduced SDR-stress-induced increases in both IL-6 and CXCL1, and significantly reduced CXCL1 and TNF-α levels in unstressed mice. This thesis has provided important information on how social stress accelerates atherosclerosis, and has suggested the release of pro-inflammatory cytokines as an underlying mechanism. Our hope is that our results, and further studies exploring mechanisms converting psychosocial stress into physical disease, will help to reduce the deleterious effects of psychosocial stress.
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| 5. |
- Johansson, Maria E, 1977, et al.
(författare)
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High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice.
- 2009
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Ingår i: Journal of hypertension. - 0263-6352 .- 0263-6352. ; 27:1, s. 41-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: High-salt diet likely elevates blood pressure (BP), thus increasing the risk of cardiovascular events. We hypothesized that a high-salt diet plays a critical role in subjects whose renin-angiotensin systems cannot adjust to variable salt intake, rendering them more susceptible to atherosclerosis. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We used urinary isoprostane as a marker for oxidative stress. RESULTS: Although high-salt diet per se did not affect plaque extension, high salt combined with Ang II increased plaque area significantly in both the aorta and the innominate artery as compared with Ang II or salt alone (P < 0.05 and P < 0.01, respectively). High-salt diet did not affect BP or isoprostane levels, whereas Ang II infusion increased both BP and isoprostane levels (P < 0.05 and P < 0.01, respectively). Although high-salt diet combined with Ang II did not amplify BP, salt in combination with Ang II increased isoprostane levels further (P < 0.001 vs. Ang II alone). Ang II increases macrophage content in lesions (P < 0.05), whereas salt likely increases collagen content. CONCLUSION: High-salt diet per se does not influence BP in ApoE-/- mice and is only moderately atherogenic. Possibly mediated via increased oxidative stress, a high-salt diet combined with fixed high Ang II levels accelerates atherogenesis synergistically, beyond the effect of BP.
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| 6. |
- Ulleryd, Marcus A, et al.
(författare)
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Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE(-/-) Mice
- 2014
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Ingår i: Biomed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
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Tidskriftsartikel (refereegranskat)abstract
- A few studies in animals and humans suggest that metoprolol (beta 1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE(-/-) mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE(-/-) mice were treated with metoprolol (2.5mg/kg/ h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P < 0.05 versus Control). Further, metoprolol reduced serum TNF alpha and the chemokine CXCL1 (P < 0.01 versus Control for both) as well as decreasing the macrophage content in the plaques (P < 0.01 versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE(-/-) mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNF alpha and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect. LAD B, 1988, AMERICAN HEART JOURNAL, V116, P322
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