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- Besga, A., et al.
(författare)
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Differences in brain cholesterol metabolism and insulin in two subgroups of patients with different CSF biomarkers but similar white matter lesions suggest different pathogenic mechanisms
- 2012
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 510:2, s. 121-126
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Tidskriftsartikel (refereegranskat)abstract
- Investigate possible associations of white matter hyperintensities (WMHs) with the metabolism of cholesterol and insulin in two subgroups of patients with memory complaints and different CSF A beta 42 and CSF tau levels. 59 patients from the memory clinic at Karolinska Hospital were included. Degree of WMHs was rated using the ARWMC scale and the following biomarkers were measured in CSF and plasma: insulin, cholesterol, lanosterol, lathosterol, and oxidized cholesterol metabolites. The WMHs in CSF control-like group correlated with increased brain cholesterol synthesis and reduced efflux of oxysterols and insulin in CSF. In the CSF AD-like group, the WMHs correlated with increased peripheral cholesterol metabolism. Despite having similar appearance on FLAIR images, the pathogenic mechanisms of WMHS are likely to be different in the two groups investigated.
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- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.
- 1996
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 97:2, s. 461-8
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Tidskriftsartikel (refereegranskat)abstract
- The presence of oxysterols in macrophages isolated from atherosclerotic tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, freshly isolated from atherosclerotic aorta, show about the same distribution of oxysterols, analyzed by isotope dilution mass spectrometry, except that all three preparations of human arterial-derived macrophages contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL expression, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on macrophage LPL mRNA expression compared with control. LPL activity in the medium was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier observation of a low level of LPL mRNA in arterial foam cells.
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- Pedrelli, M., et al.
(författare)
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Athero-protective properties of plasma lipoproteins from brown bears (URSUS ARCTOS) during hibernation and active state
- 2020
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Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 315, s. E69-E70
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Plasma cholesterol (TC) and triglyceride (TG) levels are twice as high in hibernating brown bears (Ursus arctos) than in healthy humans. Yet, bears display no signs of atherosclerosis. To explore this apparent paradox, lipoprotein structure and function of brown bears were analyzed and compared with those of healthy humans.Methods: Blood from the same wild free-ranging Swedish brown bears (n=10) was drawn during hibernation (winter) and active state (summer). Plasma lipoproteins were separated by size exclusion chromatography, ultracentrifugation and gel-electrophoresis. LDL binding to arterial proteoglycans (PGs) was measured. Data are presented as median (10th - 90th percentile).Results: During hibernation bear LDL carried 4.6 (2.3-5.9) mmol/L cholesterol esters (CE), 1.5 (1.1-2.4) mmol/L unesterified (UC), 3.7 (2.1-4.9) mmol/L TG and 2.5 (1.8-3.4) mmol/L phospholipid (PL). Human LDL were smaller than bear LDL, which were proportionally richer in TG (winter 31 (26-33)%, summer 30 (22-40)%vs human 9% (7-15); p<0.001) and had less CE (winter 36 (26-45)%, summer 25 (21-37)%vs human 48 (46-55)%; p<0.01)). Bear LDL were less positively charged and showed a pre-ß motility on agarose gel. Thus, bear LDL had about 10 times lower binding to PGs than human LDL.Conclusions: Despite high TC and TG levels, bear lipoproteins were less atherogenic than the human analogues. This was due to low LDL affinity for PGs, secondary to increased TG and PL, and to low positive charge. Our study provides further mechanistic insights for the atherosclerosis development, which is driven by the circulating lipoprotein composition and functions rather than plasma absolute lipid levels.
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