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- Beazer, Jack D., et al.
(författare)
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High-density lipoproteins vascular protective functions in metabolic and cardiovascular disease - could extracellular vesicles be at play?
- 2020
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Ingår i: Clinical Science. - : Portland Press on behalf of the Medical Research Society and the Biochemical Society. - 0143-5221 .- 1470-8736. ; 134:22, s. 2977-2986
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Forskningsöversikt (refereegranskat)abstract
- High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health - including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases - both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDLs vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.
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| 2. |
- Ross, Cody T., et al.
(författare)
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The Origins and Maintenance of Female Genital Modification across Africa
- 2016
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Ingår i: Human Nature. - : Springer Science and Business Media LLC. - 1045-6767 .- 1936-4776. ; 27:2, s. 173-200
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Tidskriftsartikel (refereegranskat)abstract
- We present formal evolutionary models for the origins and persistence of the practice of Female Genital Modification (FGMo). We then test the implications of these models using normative cross-cultural data on FGMo in Africa and Bayesian phylogenetic methods that explicitly model adaptive evolution. Empirical evidence provides some support for the findings of our evolutionary models that the de novo origins of the FGMo practice should be associated with social stratification, and that social stratification should place selective pressures on the adoption of FGMo; these results, however, are tempered by the finding that FGMo has arisen in many cultures that have no social stratification, and that forces operating orthogonally to stratification appear to play a more important role in the cross-cultural distribution of FGMo. To explain these cases, one must consider cultural evolutionary explanations in conjunction with behavioral ecological ones. We conclude with a discussion of the implications of our study for policies designed to end the practice of FGMo.
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| 3. |
- Sulaiman, Wan N Wan, et al.
(författare)
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Does high-density lipoprotein protect vascular function in healthy pregnancy?
- 2016
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 130:7, s. 491-497
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Tidskriftsartikel (refereegranskat)abstract
- The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur.
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