| 1. |
- Virta, Jenni, et al.
(författare)
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Effects of dipeptidyl peptidase 4 inhibition on inflammation in atherosclerosis : A 18F-fluorodeoxyglucose study of a mouse model of atherosclerosis and type 2 diabetes
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 305, s. 64-72
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes. Methods: Igf2/Ldlr−/−Apob100/100 mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks. Five mice fed a chow diet were studied as an additional control. At the end of the study, glucose tolerance, aortic and liver uptake of 18F-FDG, and histology were studied. Results: Mice in linagliptin and HFD groups had similar fasting glucose concentrations, but linagliptin improved glucose tolerance. Aortas of linagliptin and HFD groups showed advanced atherosclerotic plaques with no difference in the mean intima-to-media ratio or number of macrophages in the plaques. Autoradiography showed similar 18F-FDG uptake by atherosclerotic plaques in linagliptin and HFD groups (plaque-to-wall ratio: 1.7 ± 0.25 vs. 1.6 ± 0.21; p = 0.24). In the liver, linagliptin reduced the histologic inflammation score but had no effect on 18F-FDG uptake. Compared with chow diet, uptake of 18F-FDG was similar in the aorta, but higher in the liver after HFD. Conclusions: Linagliptin therapy improved glucose tolerance and reduced hepatic inflammation but had no effect on plaque burden or atherosclerotic inflammation, as determined by histology and 18F-FDG uptake, in atherosclerotic mice with type 2 diabetes.
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| 2. |
- Andersson, Annelie, 1971-, et al.
(författare)
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Behaviour of European wild boars (Sus scrofa) in connection with farrowing in an enclosure
- 2011
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Ingår i: Mammalian Biology. - : Elsevier. - 1616-5047 .- 1618-1476. ; 76:3, s. 332-338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Wild boars (Sus scrofa) are often kept in enclosures for hunting or meat production purposes in Sweden. The sows are known to undergo behavioural changes in connection with farrowing and their natural behaviours may be compromised by the limited area of the enclosure. The aim of this study was to quantitatively describe wild boar sows’ behaviour when farrowing in an enclosure. A field study was carried out in a hunting enclosure, where 1200 hours of behavioural recordings and data from 22 farrowings were collected. According to the results, the farrowing period could be divided into 3 phases: pre-farrowing, isolation and sociality phases (in relation to farrowing: day -14 to -1, day 1 to 8, day 9 to 14 respectively). The activity decreased during isolation and increased in the sociality phase (p<0.05), whereas the average distance to other individuals increased during isolation and decreased in the sociality phase (p<0.05). Nose contacts with other individuals increased in the isolation phase (p<0.05) and habitat use changed towards more protective habitats after farrowing. 68 % of the nests were situated in edges between two habitats of different vegetation density and 73% had some kind of protection to the north. We conclude that farrowing induces a number of changes in the activity, social behaviour and habitat preference in captive European wild boars. This may need attention when enclosures for this species are designed.
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| 3. |
- Gallini, Radiosa, et al.
(författare)
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Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells in vertebrate development. To what extent PDGFs also exert beneficial homeostatic or reparative roles in adult organs, as opposed to adverse fibrogenic responses in pathology, are unclear. PDGF signaling plays critical roles during heart development, during which forced overexpression of PDGFs induces detrimental cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct myocardial repair. Different PDGFs may exert different effects mediated through the two PDGF receptors (PDGFR alpha and PDGFR beta) in different cell types. Here, we assessed responses induced by five known PDGF isoforms in the adult mouse heart in the context of adenovirus vector-mediated inflammation. Our results show that different PDGFs have different, in some cases even opposing, effects. Strikingly, whereas the major PDGFRa agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFR alpha-positive fibroblasts, PDGFR beta agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirusinduced inflammation and produced a small and dense scar (PDGF-D). These results provide evidence for PDGF isoform-specific inflammation-modulating functions that may have therapeutic implications. They also illustrate a surprising complexity in the PDGF-mediated pathophysiological responses.
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| 4. |
- Hagberg, Carolina E, et al.
(författare)
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Vascular endothelial growth factor B controls endothelial fatty acid uptake.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7290, s. 917-21
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Tidskriftsartikel (refereegranskat)abstract
- The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb(-/-) mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.
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