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- Saliba-Gustafsson, P., et al.
(författare)
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Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 660-675
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Tidskriftsartikel (refereegranskat)abstract
- Background Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. Objective We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. Methods A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. Results The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. Conclusions For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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| 2. |
- Bonomi, A, et al.
(författare)
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Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study
- 2020
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Ingår i: Genes and immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 21:2, s. 100-108
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Tidskriftsartikel (refereegranskat)abstract
- The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–maxβ = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
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| 4. |
- Lupattelli, A., et al.
(författare)
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Medication use in pregnancy: a cross-sectional, multinational web-based study
- 2014
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants Pregnant women and new mothers with children less than 1year of age. Primary and secondary outcome measures Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. Conclusions In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.
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| 6. |
- Mårdby, Ann-Charlotte, 1976, et al.
(författare)
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Consumption of alcohol during pregnancy-A multinational European study
- 2017
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Ingår i: Women and Birth. - : Elsevier BV. - 1871-5192. ; 30:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although single-country studies indicate alcohol consumption among some pregnant European women, it is difficult to interpret European differences. Few multinational studies exist using the same methodology. Aim: To estimate the proportion of women consuming alcohol during pregnancy in Europe, and to analyze whether between country variations could be explained by sociodemography and smoking. Methods: An anonymous online questionnaire was accessible for pregnant women and new mothers in 11 European countries during two months between October 2011 and February 2012 in each country. The questionnaire covered alcohol consumption, sociodemographic factors, and smoking habits during pregnancy. Descriptive analyses and logistic regression models were conducted. Findings: The study population consisted of 7905 women, 53.1% pregnant and 46.9% new mothers. On average, 15.8% reported alcohol consumption during pregnancy. The highest proportion of alcohol consumption during pregnancy was found in the UK (28.5%), Russia (26.5%), and Switzerland (20.9%) and the lowest in Norway (4.1%), Sweden (7.2%), and Poland (9.7%). When reporting alcohol consumption during pregnancy, 39% consumed at least one unit per month. In Italy, Switzerland, and the UK, over half consumed at least one alcohol unit per month. Higher education and smoking before pregnancy were predictors of alcohol consumption during pregnancy. Conclusions: Almost 16% of women resident in Europe consumed alcohol during pregnancy with large cross-country variations. Education and smoking prior to pregnancy could not fully explain the differences between the European countries. A united European strategy to prevent alcohol consumption during pregnancy is needed with focus on countries with the highest consumption. (C) 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
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