| 1. |
- Adiels, Martin, 1976, et al.
(författare)
-
Postprandial accumulation of chylomicrons and chylomicron remnants is determined by the clearance capacity.
- 2012
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 222:1, s. 222-8
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To better understand the postprandial clearance of triglyceride-rich lipoproteins (TRLs) and its relation to the fasting kinetics of TRLs. Methods Two studies were performed on 30 male subjects: a fasting kinetic study to determine the fasting secretion and clearance rates of apolipoprotein B (apoB) 100 and triglycerides in the very low-density lipoprotein 1 and 2 (VLDL1 and VLDL2) fractions; and a postprandial study to determine the postprandial accumulation of apoB48, apoB100 and triglycerides in the chylomicron, VLDL1 and VLDL2 fractions. Results from these two studies were combined to characterize the postprandial clearance of TRLs in a physiologically relevant setting. Results Our results show that postprandial accumulation of the apoB48-carrying chylomicrons can be predicted from the clearance capacity of the lipolytic pathway, determined in the fasting state. Furthermore, we show that chylomicrons and VLDL1 particles are not cleared equally by the lipoprotein lipase pathway, and that chylomicrons seem to be the preferred substrate. Subjects with a rapid fasting lipid metabolism accumulate lower levels of postprandial triglycerides with less accumulation of apoB100 in the VLDL1 fraction and a faster transfer of apoB100 into the VLDL2 fraction. In contrast, fasting VLDL1 secretion does not predict postprandial triglyceride accumulation. Conclusions Non-fasting triglyceride levels have recently been identified as a major predictor of future cardiovascular events. Here we show that the capacity of the lipolytic pathway is a common determinant of both the fasting and non-fasting triglyceride levels and may thus play an important role in the development of dyslipemia and atherosclerosis.
|
|
| 2. |
- Andersson, J., et al.
(författare)
-
Echogenecity of the carotid intima-media complex is related to cardiovascular risk factors, dyslipidemia, oxidative stress and inflammation The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2009
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 204:2, s. 612-618
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Increased carotid artery intima-media thickness (IMT), measured by ultrasound, is related to an increased risk of cardiovascular disease. Since presence of echolucent plaques increases the risk further, we investigated if echogenecity of the carotid intima-media complex is related to markers of cardiovascular risk. Our aim was therefore to investigate if intima-media echogenecity is related to cardiovascular risk factors, or to markers of inflammation and oxidation in an exploratory investigation. Methods: The PIVUS cohort study is an observational study of 1016 (509 women and 507 men) randomly chosen individuals aged 70 living in Uppsala, Sweden. Carotid artery ultrasound measurements were performed. IMT and the grey scale median (GSM) value were calculated in the intima-media complex (IM-GSM) in the far wall of the common carotid artery. Traditional risk factors were evaluated together with indices of oxidative stress and inflammation. Results: In the multiple regression analysis, HDL-cholesterol, body mass index, conjugated diens, glutathione, e-selectin and TNF alfa were significantly related to IM-GSM. IMT was independently related to blood pressure, smoking and body mass index. Conclusion: The echolucency of the carotid intima-media was related to several cardiovascular risk factors not related to IMT, such as dyslipidemia, oxidative stress and inflammation. Since the echogenecity of the carotid intima-media complex was related to different risk factors compared to carotid IMT, it is worthwhile to further explore the usefulness of this new marker of the vascular wall. (C) 2009 Published by Elsevier Ireland Ltd.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Hägg, Daniel, 1974, et al.
(författare)
-
Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible IL-6-CD44 feedback loop?
- 2007
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 190:2, s. 291-7
-
Tidskriftsartikel (refereegranskat)abstract
- The cell-adhesion molecule CD44 likely participates in atherosclerosis development. We have shown previously that pro-inflammatory cytokines affect CD44 expression. Therefore, this work examined the role of elevated CD44 levels in human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed elevated levels of CD44 transcript and protein (1.5-fold) compared to matched controls (n=15) (P=0.050 and 0.044, respectively). To test whether genetic factors influence CD44 expression, two single nucleotide polymorphisms in the CD44 gene were analyzed but these were not associated with coronary artery disease. We also examined the potential connection between plasma cytokine levels and CD44 expression. In atherosclerotic subjects, elevated CD44 expression correlates (P=0.012) with enhanced macrophage IL-6 secretion (3.13+/-2.5 pg/mL versus 0.32+/-0.16 pg/mL in controls, P=0.021). Additionally, CD44-deficient mice exhibit less circulating IL-6 than wild-type controls (9.8+/-0.7 pg/mL versus 14.3+/-0.7 pg/mL; P=0.032). Furthermore, IL-6 augments CD44 expression in primary human macrophages after 24 h (P=0.038) and 48 h (P=0.015). Taken together, our data show an IL-6-CD44 feedback loop in macrophages. Such a positive feedback loop may aggravate atherosclerosis development.
|
|
| 6. |
- Hägg, Daniel, 1974, et al.
(författare)
-
Expression of chemokine (C-C motif) ligand 18 in human macrophages and atherosclerotic plaques
- 2009
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 204:2
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Using gene expression profiling, we aimed to identify genes that are predominantly expressed in human carotid atherosclerotic plaques. Such genes may be important in atherogenesis and pathophysiology of the plaque, and genes that encode for secreted proteins may be potential biomarkers for atherosclerosis and cardiovascular disease. METHODS: DNA microarray generated expression profiles of human carotid atherosclerotic plaques were compared to expression profiles of 80 different human tissues and cell types, to identify plaque-specific genes. RESULTS: We identified the chemokine (C-C motif) ligand 18 (CCL18) as predominantly expressed in human carotid plaque. Immunohistochemistry showed that CCL18 protein was localized to a subset of macrophages in carotid plaques. Monocyte-derived macrophages from subjects with atherosclerosis had threefold higher expression of CCL18 than macrophages from control subjects (p=0.012). Subjects with A/G genotype of the rs2015086 SNP in the promoter region of the CCL18 gene had threefold higher macrophage expression of CCL18 than subjects with A/A genotype (p=0.049), but we found no association of this SNP with an increased risk of coronary heart disease. We also compared serum levels of CCL18 from subjects with symptomatic carotid artery disease with control subjects. There were no differences in serum levels of CCL18 between the two groups, however CCL18 correlated with measurements of adiposity. CONCLUSION: CCL18 is predominantly expressed in human atherosclerotic plaques and may participate in the atherosclerotic plaque formation.
|
|
| 7. |
- Hägg, Daniel, 1974, et al.
(författare)
-
Oxidized LDL induces a coordinated up-regulation of the glutathione and thioredoxin systems in human macrophages.
- 2006
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 185:2, s. 282-9
-
Tidskriftsartikel (refereegranskat)abstract
- Using DNA microarray analysis, we found that human macrophages respond to oxidized low-density lipoprotein (oxLDL) by activating the antioxidative glutathione and thioredoxin systems. Several genes of the glutathione and thioredoxin systems were expressed at high levels in macrophages when compared to 80 other human tissues and cell types, indicating that these systems may be of particular importance in macrophages. The up-regulation of three genes in these systems, thioredoxin (P < 0.005), thioredoxin reductase 1 (P < 0.001) and glutathione reductase (P < 0.001) was verified with real-time RT-PCR, using human macrophages from 10 healthy donors. To investigate the possible role of these antioxidative systems in the development of atherosclerosis, expression levels in macrophages from 15 subjects with atherosclerosis (12 men, 3 women) and 15 matched controls (12 men, 3 women) were analyzed using DNA microarrays. Two genes in the glutathione system Mn superoxide dismutase (P < 0.05) and catalase (P < 0.05) differed in expression between the groups. We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.
|
|
| 8. |
- Lanuza, Fabian, et al.
(författare)
-
Plasma metabolomic profiles of plant-based dietary indices reveal potential pathways for metabolic syndrome associations
- 2023
-
Ingår i: Atherosclerosis. - 1879-1484 .- 0021-9150. ; 382
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Plant-based dietary patterns have been associated with improved health outcomes. This study aims to describe the metabolomic fingerprints of plant-based diet indices (PDI) and examine their association with metabolic syndrome (MetS) and its components in a Danish population. Methods: The MAX study comprised 676 participants (55% women, aged 18-67 y) from Copenhagen. Sociodemographic and dietary data were collected using questionnaires and three 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). Mean dietary intakes were computed, as well as overall PDI, healthful (hPDI) and unhealthful (uPDI) scores, according to food groups for each plant-based index. Clinical variables were also collected at the same time points in a health examination that included complete blood tests. MetS was defined according to the International Diabetes Federation criteria. Plasma metabolites were measured using a targeted metabolomics approach. Metabolites associated with PDI were selected using random forest models and their relationships with PDIs and MetS were analyzed using generalized linear mixed models. Results: The mean prevalence of MetS was 10.8%. High, compared to low, hPDI and uPDI scores were associated with a lower and higher odd of MetS, respectively [odds ratio (95%CI); hPDI: 0.56 (0.43–0.74); uPDI: 1.61 (1.26–2.05)]. Out of 411 quantified plasma metabolites, machine-learning metabolomics fingerprinting revealed 13 metabolites, including food and food-related microbial metabolites, like hypaphorine, indolepropionic acid and lignan-derived enterolactones. These metabolites were associated with all PDIs and were inversely correlated with MetS components (p < 0.05). Furthermore, they had an explainable contribution of 12% and 14% for the association between hPDI or uPDI, respectively, and MetS only among participants with overweight/obesity. Conclusions: Metabolites associated with PDIs were inversely associated with MetS and its components, and may partially explain the effects of plant-based diets on cardiometabolic risk factors.
|
|
| 9. |
- Lind, Lars, et al.
(författare)
-
The echogenecity of the intima-media complex in the common carotid artery is closely related to the echogenecity in plaques.
- 2007
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 195:2, s. 411-414
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The echogenecity measured by ultrasound of atherosclerotic plaques is related to future cardiovascular events. The aim of the present study is to relate the grey scale median of the intima–media complex (IM-GSM) of the common carotid artery (CCA) to the echogenecity of carotid plaques. Material and results In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, carotid artery intima–media thickness (IMT) and IM-GSM were evaluated by ultrasound and computerized analysis. Also the occurrence of plaque and plaque GSM were measured. The echogenecity of the plaques was also visually estimated by the Gray-Weale classification. In subjects with a carotid plaque (n=582), IM-GSM in CCA was correlated to GSM in the plaque (r=0.60, p<0.0001) independently of plaque size and IMT. IM-GSM in CCA was also correlated to the visually estimated echogenecity (p<0.0001 for trend). Conclusion IM-GSM of the CCA is closely related to the echogenecity in overt carotid plaques, regardless if evaluated by the same computerized method or evaluated visually. This finding suggests that IM-GSM of CCA could be an important and easily measurable characteristic of the carotid artery wall that could be obtained in almost all subjects and not only those with an overt plaque.
|
|
| 10. |
- Lindqvist, Helen, 1977, et al.
(författare)
-
Plasma phospholipid EPA and DHA in relation to atherosclerosis in 61-year-old men
- 2009
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 205:2, s. 574-578
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been shown to decrease the risk for cardiovascular death and to reduce CVD risk factors. It has also been suggested that EPA and DHA reduce atherosclerosis progression, but data are inconclusive. Carotid intima-media thickness (IMT) is a well-established surrogate measure for sub-clinical atherosclerosis. Our aim was to examine if plasma phospholipid EPA and DHA are associated with IMT and plaque occurrence and size in the carotid and femoral arteries. Methods: IMT and plaque occurrence in carotid and femoral arteries was measured by ultrasound in 487 sixty-one-year-old men in this cross-sectional study. Plasma phospholipid levels of EPA and DHA, serum lipids, cell adhesion molecules, and blood pressure were measured, and occurrence of diabetes and socioeconomic factors were assessed. Results: Plasma phospholipid EPA was negatively associated with IMT in carotid and femoral arteries, and with cigarette years and cell adhesion proteins. EPA was positively associated with HDL, total cholesterol, blood pressure, plasma insulin and years of education. The association between EPA and carotid IMT remained after adjustment for blood pressure, but not for other covariates. Plasma phospholipid DHA was negatively associated with cigarette years and several endothelial markers, and positively associated with years of education and systolic blood pressure. In contrast to other studies, EPA content was higher in diabetic patients compared with patients without diabetes. Conclusion: Plasma phospholipid EPA, but not DHA, was inversely associated with carotid and femoral IMT, as well as several endothelial markers supporting the concept of an effect of EPA on the vascular wall. This association was independent of blood pressure, but not for other covariates. There was no association between plasma phospholipid EPA or DHA and plaque occurrence in the carotid and femoral arteries. © 2008 Elsevier Ireland Ltd. All rights reserved.
|
|
