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Sökning: WFRF:(Rudling M)

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  • Galman, C, et al. (författare)
  • Age-induced hypercholesterolemia in the rat relates to reduced elimination but not increased intestinal absorption of cholesterol
  • 2007
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 293:3, s. E737-E742
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma cholesterol increases in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol as bile acids (BAs) and decreased receptor-mediated clearance of plasma LDL, changes that can be reversed by treatment with growth hormone (GH). The level of intestinal absorption of cholesterol may also contribute to the development of hypercholesterolemia. In this study, we investigated whether cholesterol absorption increases with age and whether any such age-related change could be influenced by treatment with GH or ezetimibe (EZE). Male rats aged 6 and 18 mo were studied with and without GH or EZE treatment. BA synthesis was reduced and plasma cholesterol was increased in the old animals, whereas cholesterol absorption was unaltered. Cholesterol absorption was not altered by GH treatment but was reduced by EZE in both groups of animals. Hepatic LDL receptors (LDLRs), scavenger receptor class B type 1, and proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) transcripts were unchanged in old animals. GH treatment induced LDLRs, PCSK9 transcripts, and BA synthesis. We conclude that the age-induced hypercholesterolemia in the rat and its reversal by GH treatment relates to altered degradation of cholesterol in the liver and is not due to changes in cholesterol absorption.
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  • Klingenberg, Roland, et al. (författare)
  • Depletion of FOXP3(+) regulatory T cells promotes hypercholesterolemia and atherosclerosis
  • 2013
  • Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 123:3, s. 1323-1334
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define the role of FOXP3-expressing Tregs in atherosclerosis, we used the DEREG mouse, which expresses the diphtheria toxin (DT) receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3(+) Tregs. Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3(+) Tregs. Depletion of Tregs caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. These mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. These results demonstrate that FOXP3(+) Tregs inhibit atherosclerosis by modulating lipoprotein metabolism.
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  • Lind, S, et al. (författare)
  • Autosomal recessive hypercholesterolaemia : Normalization of plasma LDL cholesterol by ezetimibe in combination with statin treatment
  • 2004
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 256:5, s. 406-412
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Severe hereditary hypercholesterolaemia is most frequently due to familial hypercholesterolaemia (FH), caused by mutations in the LDL receptor (LDLR) gene. However, a phenotype very similar to FH may also be caused by defects in other genes like the genes for apolipoprotein (apo) B-100 or autosomal recessive hypercholesterolaemia (ARH). Subject. An 8-year-old male of Lebanese origin was diagnosed with severe hypercholesterolaemia and extensive cutaneous and tendon xanthomas. Plasma LDL cholesterol before treatment was 17 mmol L-1, whilst parents and both siblings had normal levels. Diagnosis. Degradation of 125I-labelled LDL in blood lymphocytes was reduced, but not abolished. Sequencing analysis of the LDLR and apoB-100 genes were negative, whilst a splice acceptor mutation in intron 1 (IVS 1 - 1G>C) was detected in the ARH gene. The patient was homozygous for the mutation, whilst the parents were heterozygous. These findings were in agreement with a diagnosis of ARH. Treatment and clinical course. Monthly LDL apheresis and atorvastatin 120 mg daily reduced LDL cholesterol preapheresis level to 4.8 mmol L-1. When ezetimibe was given 10 mg day-1 in combination with rosuvastatin 80 mg day-1, LDL cholesterol was further lowered to 1.6 mmol L-1, which made apheresis unnecessary. Cutaneous and tendon xanthomas disappeared completely and the intima-media thickness of the common carotid arteries decreased. At age 23 he developed a small myocardial infarction. Conclusion. ARH should be considered in cases of severe hypercholesterolaemia with a pattern of recessive inheritance. Combination therapy with high-dose statin and ezetimibe seems to be the treatment of choice in ARH and may reduce or eliminate the need for LDL apheresis treatment.
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  • Matasconi, M, et al. (författare)
  • Pituitary control of lipoprotein and bile acid metabolism in male rats: growth hormone effects are not mediated by prolactin
  • 2004
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 287:1, s. E114-E119
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have established that growth hormone (GH) has many important effects on the regulation of cholesterol and lipoprotein metabolism. However, human GH (hGH) can also bind to prolactin receptors, eliciting prolactin receptor-mediated effects. In this study, we evaluated whether hGH can exert such responses in currently used animal models and whether prolactin affects lipoprotein and/or hepatic cholesterol metabolism. Normal and hypophysectomized (Hx) male rats were given either hGH or bovine GH, the latter unable to bind to the prolactin receptor. The hormones were continuously infused by use of subcutaneous osmotic mini-pumps for 7 days; blood and livers were collected after euthanasia. Both hormones stimulated hepatic LDL receptor expression and bile acid synthesis to a similar extent and normalized the altered plasma lipoprotein pattern in Hx rats. Prolactin, injected twice daily to Hx male rats, did not exert any effects on the plasma lipoprotein pattern or on cholesterol metabolism. We conclude that previously established effects of hGH on cholesterol metabolism are not mediated by prolactin in male rats.
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  • Mårtensson, Olof, et al. (författare)
  • Effects of fermented, ropy, non-dairy, oat-based products on serum lipids and the faecal excretion of cholesterol and short chain fatty acids in germfree and conventional rats
  • 2002
  • Ingår i: Nutrition Research. - 0271-5317. ; 22:12, s. 1461-1473
  • Tidskriftsartikel (refereegranskat)abstract
    • Three fermented, ropy, non-dairy, oat-based products were evaluated for their effect on serum lipids, faecal cholesterol and faecal short chain fatty. acids in germfree and conventional rats. Three different exopolysaccharide (EPS) producing lactic acid bacteria strains were used to ferment the non-dairy oat-base (Adavena(R) G40) (Ceba Foods AB, Lund; Sweden). Two commercial non-dairy products based on oats (Mill Milk(TM)) (Ceba Foods AB, Lund, Sweden) and rice (Rice Dream(R)) (Imagine Foods, London, UK) were used as non-ropy and unfermented controls. All the standardized feeds were sterilized before being fed to the animals. Adult, germfree-and conventional AGUS rats, were fed the above sterile diets ad libitum for 21 days. Blood samples and faecal samples were collected and the animals' weight gain was monitored throughout the study. No significant change in serum lipids or faecal excretion of cholesterol was observed between the groups on the different diets. A difference in faecal SCFA pattern was observed in conventional rats fed on the oat-based diets in comparison. to the group fed on the rice-based diet. More evidence is needed to support the effect of fermented, ropy, oat-based products and their potential effect on serum lipids, faecal cholesterol/coprostanol levels and amounts of short chain fatty acids.
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