| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Pedrelli, M., et al.
(författare)
-
Athero-protective properties of plasma lipoproteins from brown bears (URSUS ARCTOS) during hibernation and active state
- 2020
-
Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 315, s. E69-E70
-
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.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Umaerus, M., et al.
(författare)
-
HDL2 interferes with LDL association with arterial proteoglycans: A possible athero-protective effect
- 2012
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 225:1, s. 115-120
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: High levels of large HDL (HDL2) reduce cardiovascular disease risks apparently because it mediates reverse cholesterol transport, and it has anti-inflammatory properties. Here we explored the mechanism behind an additional athero-protective HDL effect related to its capacity to interfere with formation of insoluble LDL-proteoglycans associations, a key step in LDL entrapment in the intima and in atherogenesis. Methods and results: We found that HDL2 levels from type 2 diabetes patients and controls are inversely correlated with complex formation between serum LDL and the arterial proteoglycans versican. Reconstitution experiments indicate that HDL2 was more efficacious inhibitor of the LDL-versican association than the smaller HDL3. This may explain why serum from patients with dyslipidemia of insulin resistance, with low levels of HDL2, have a higher capacity to form insoluble LDL-proteoglycan complex. ApoE enrichment of HDL2 and HDL3 or addition of copies of an apoE peptide with the proteoglycan-binding sequence of this apolipoprotein increased their inhibition of LDL-versican associations. Conclusions: The inhibitory effect of HDL2 and HDL3 on LDL-versican associations was related to formation of apoE-mediated soluble HDL-versican complexes. We speculate that in the intima large, HDL2 subclasses, by forming reversible soluble associations with proteoglycans can compete with formation of irreversible LDL-proteoglycan aggregates. This can contribute to the HDL2 athero-protective effects. In the dyslipidemia of insulin resistance, associated with low levels of HDL2, this athero-protective property may be compromised. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
|
|
| 9. |
|
|
| 10. |
- Berg, M, et al.
(författare)
-
3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr-/- mice
- 2020
-
Ingår i: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 116:12, s. 1948-1957
-
Tidskriftsartikel (refereegranskat)abstract
- AimsAtherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two major signalling pathways, activation of SREBPs and inflammasome, are associated with the 3-HAA-dependent regulation of lipoprotein synthesis and inflammation in the atherogenesis process. Moreover, we examined whether inhibition of endogenous 3-HAA degradation affects hyperlipidaemia and plaque formation.Methods and resultsIn vitro, we showed that 3-HAA reduces SREBP-2 expression and nuclear translocation and apolipoprotein B secretion in HepG2 cell cultures, and inhibits inflammasome activation and IL-1β production by macrophages. Using Ldlr−/− mice, we showed that inhibition of 3-HAA 3,4-dioxygenase (HAAO), which increases the endogenous levels of 3-HAA, decreases plasma lipids and atherosclerosis. Notably, HAAO inhibition led to decreased hepatic SREBP-2 mRNA levels and lipid accumulation, and improved liver pathology scores.ConclusionsWe show that the activity of SREBP-2 and the inflammasome can be regulated by 3-HAA metabolism. Moreover, our study highlights that targeting HAAO is a promising strategy to prevent and treat hypercholesterolaemia and atherosclerosis.
|
|
