Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Akkermansia muciniphila Exerts Lipid-Lowering and Immunomodulatory Effects without Affecting Neointima Formation in Hyperlipidemic APOE*3-Leiden.CETP Mice
Katiraei, Saeed ; Vries, Margreet R. de; Costain, Alice H. ; Thiem, Kathrin ; Hoving, Lisa R. ; Diepen, Janna A. van; Smits, Hermelijn H. ; Bouter, Kristien E. ; Rensen, Patrick C.N. ; Quax, Paul H.A. ; Nieuwdorp, Max ; Netea, Mihai G. ; Vos, Willem M. de; Cani, Patrice D. ; Belzer, Clara ; Dijk, Ko Willems van; Berbée, Jimmy F.P. ; Harmelen, Vanessa van - \ 2019
Molecular Nutrition & Food Research (2019). - ISSN 1613-4125
Akkermansia muciniphila - atherosclerosis - immunity - lipid metabolism - mesenteric lymph nodes

Scope: Akkermansia muciniphila (A. muciniphila) is an intestinal commensal with anti-inflammatory properties both in the intestine and other organs. The aim is to investigate the effects of oral administration of A. muciniphila on lipid metabolism, immunity, and cuff-induced neointima formation in hyperlipidemic APOE*3-Leiden (E3L).CETP mice. Methods and results: Hyperlipidemic male E3L.CETP mice are daily treated with 2 × 108 CFU A. muciniphila by oral gavage for 4 weeks and the effects are determined on plasma lipid levels, immune parameters, and cuff-induced neointima formation and composition. A. muciniphila administration lowers body weight and plasma total cholesterol and triglycerides levels. A. muciniphila influences the immune cell composition in mesenteric lymph nodes, as evident from an increased total B cell population, while reducing the total T cell and neutrophil populations. Importantly, A. muciniphila reduces the expression of the activation markers MHCII on dendritic cells and CD86 on B cells. A. muciniphila also increases whole blood ex vivo lipopolysaccharide-stimulated IL-10 release. Finally, although treatment with A. muciniphila improves lipid metabolism and immunity, it does not affect neointima formation or composition. Conclusions: Four weeks of treatment with A. muciniphila exerts lipid-lowering and immunomodulatory effects, which are insufficient to inhibit neointima formation in hyperlipidemic E3L.CETP mice.

Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in Ldlr-/- mice
Hendrikx, Tim ; Jeurissen, M.L.J. ; Gorp, P.J. Van; Gijbels, M.J. ; Walenbergh, S.M.A. ; Houben, Tom ; Gorp, Rick Van; Pöttgens, C.C. ; Stienstra, Rinke ; Netea, M.G. ; Hofker, M.H. ; Donners, M.M.P.C. ; Shiri-Sverdlov, Ronit - \ 2015
FEBS Journal 282 (2015)12. - ISSN 1742-464X - p. 2327 - 2338.
atherosclerosis - cardiovascular diseases - caspase-1/11 - inflammasome - macrophage

Recent investigations have suggested that inflammasome activation plays an important role during atherosclerosis. Upon activation, the inflammasome induces processing and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) via activation of caspase-1/11. Previously, it was shown that complete caspase-1 deficiency is protective against atherosclerosis development. However, while macrophages are the main inflammatory cells involved in atherosclerosis, the exact role of macrophage-specific caspase-1/11 activation during development of cardiovascular disease has never been investigated. We hypothesized that hematopoietic caspase-1/11 deficiency leads to reduced atherosclerosis development. To investigate the specific contribution of hematopoietic caspase-1/11 activation to atherosclerosis development, Ldlr-/- mice received a transplant (tp) of wild-type (WT) or caspase-1/11-/- bone marrow, to create WT-tp mice and caspase-1/11-/--tp mice, and fed a high-fat, high-cholesterol diet for 12 weeks. Our results showed an increase in anti-inflammatory blood leukocytes in caspase-1/11-/--tp mice compared with WT-tp mice, as indicated by a decreased level of Ly6Chigh monocytes and an increased level of Ly6Clow monocytes. In line with our hypothesis, hematopoietic deletion of caspase-1/11 resulted in a strong reduction in atherosclerotic plaque size. Furthermore, necrotic core content was dramatically decreased in caspase-1/11-/--tp mice. Our data indicate that hematopoietic caspase-1/11 activation is involved in vascular inflammation and atherosclerosis, and plays an important role in cardiovascular disease progression. In this study, we investigated the contribution of hematopoietic caspase-1/11 to atherosclerosis development by transferring wild-type or caspase-1/11 deficient bone marrow cells into hyperlipidemic Ldlr-/- recipient mice. Hematopoietic deletion of caspase-1/11 resulted in smaller plaque size and reduced cell death in the plaque area compared to controls. These data indicate that hematopoietic caspase-1/11 activation plays an important role in vascular inflammation and atherosclerosis.

Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality
Sijtsma, F.P.C. - \ 2015
Wageningen University. Promotor(en): Daan Kromhout; D.R. Jacobs, co-promotor(en): Sabita Soedamah-Muthu. - Wageningen : Wageningen University - ISBN 9789462575493 - 207
dieet - hart- en vaatziekten - atherosclerose - prognostische merkers - ziektemerkers - mortaliteit - classificatiesystemen - epidemiologie - longitudinaal onderzoek - diet - cardiovascular diseases - atherosclerosis - prognostic markers - disease markers - mortality - classification systems - epidemiology - longitudinal studies

Summary belonging to the thesis entitled ‘Dietary patterns, biomarkers of atherosclerosis, cardiovascular and all-cause mortality’

The long history of epidemiologic studies on diet and cardiovascular disease (CVD) has traditionally relied on analysis of specific nutrients or foods. Dietary patterns are multiple dietary components operationalized as a single exposure; they reflect the entire diet. In general, two methods are used to define dietary patterns: 1) theoretically, or a priori, defined dietary scores and 2) empirically, or a posteriori, derived dietary patterns. A priori dietary scores were developed to assess diet quality based on adherence to dietary patterns or recommendations. An example of an ‘a posteriori’ approach is factor analysis (e.g. principal components analysis (PCA)). Factor analysis reduces data into patterns based upon intercorrelations between nutrients or foods. The aim of this thesis was to create, examine and compare several dietary patterns and indices and assess these in relation to both early stage markers of CVD (markers of endothelial function and oxidative stress) and to mortality from CVD and all-causes.

In chapter 2 we described the creation of the A Priori Diet Quality Score, representing overall diet quality in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The CARDIA study included 5115 black and white men and women, aged 18-30 at baseline (1985-86). Diet was assessed diet at baseline, year 7(1992-93) and 20 (2005-06) examinations. The A Priori Diet Quality Score summed 46 food groups rated by investigators as positive or negative on the basis of hypothesized health effects. In 2652 participants with 3 diet assessments, the mean (±SD) A Priori Diet Quality Score increased from 64.1± 13.0 at year 0 to 71.1 ± 12.6 at year 20, which was primarily attributable to increased age. However, the secular trend, which was estimated from differences of dietary quality scores across time at a fixed age (age matched time trend), decreased. The diet score was higher in whites than in blacks and in women than in men and increased with education, but demographic gaps in the score narrowed over 20 y. Consumption of positively rated food groups tended to increase and negatively rated food groups tended to decrease, and were similar in direction across demographic groups.

In chapter 3 we used the ‘A Priori Diet Quality Score’ and two dietary patterns derived using principal components analysis (PCA) the ‘Fruit and Vegetables’ dietary pattern and the ‘Meat’ dietary pattern in the CARDIA study. We studied prospective associations of the ‘A Priori Diet Quality Score’, the ‘Fruit and Vegetables’ dietary pattern and the ‘Meat’ dietary pattern with cellular adhesion molecules (CAMs). The ‘Fruit and Vegetables’ dietary pattern was characterized by high intakes of fruit, vegetables, and whole grains and the ‘Meat’ dietary pattern by high intakes of red meat, refined grain, and butter. The ‘A Priori Diet Quality Score’ was related to all CAMs. The ‘Fruit and Vegetables’ dietary pattern was related to E-selectin and sICAM-1 but not to P-selectin and VCAM. The ‘Meat’ dietary pattern was related to all CAMs except VCAM. Strongest associations were for the ‘Meat’ dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the ‘A Priori Diet Quality Score’ with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)).

Chapter 4 described prospective associations of the A Priori Diet Quality Score, ‘Fruit and Vegetables’ dietary pattern and ‘Meat’ dietary pattern and a plasma biomarker of lipid peroxidation, F2-isoprostanes also in the CARDIA study. We estimated associations between each dietary pattern and plasma F2-isoprostanes cross-sectionally (at year 20, n=2736) and prospectively (year 0/7 average diet and year 15/20 average F2-isoprostanes, n=2718). In the cross-sectional analysis, the A Priori Diet Quality Score and the ‘Fruit and Vegetables’ dietary pattern were inversely, and the ‘Meat’ dietary pattern was positively, associated with F2-isoprostanes (all p values <0.001). These associations were also statistically significant in prospective analysis.

In chapter 5 we described a food classification system derived from the Food-based Dietary Guidelines in the Netherlands that can be used to systematically and objectively classify foods in relation to their effects on health. Classification criteria for each food group were developed based on presumed positive, neutral or negative effects on chronic diseases of five nutrients: four that likely increase (saturated fatty acids, mono-trans unsaturated fatty acids, sodium, and added sugar) and one that likely decreases (dietary fiber) the risk of chronic diseases. This classification system also provided a framework to create food-based dietary scores for epidemiologic research on diet and chronic disease relationships.

Chapter 6 describes the creation of two dietary scores the ‘Dutch Healthy Nutrient and Food Score’ and the ‘Dutch Undesirable Nutrient and Food Score’ based on the food classification system described in chapter 5 in the Alpha Omega Trial. The Alpha Omega Trial is a randomized controlled trial; however the current analyses were done from an observational prospective cohort perspective (with adjustment for intervention groups). We included 4307 cardiac patients aged 60-80 years and monitored mortality for 10 years. Patients in the highest quintile of the ‘Dutch Healthy Nutrient and Food Score’ had 30% (HR 0.70; 95% CI 0.55-0.91) lower CVD and 32% (HR 0.68; 95%CI 0.47-0.99) lower all-cause mortality risk compared to patients in the first quintile. The ‘Dutch Undesirable Nutrient and Food Score’ was unrelated to both CVD and all-cause mortality.

In Chapter 7 we also created a ‘Dutch Healthy Nutrient and Food Score’ and a ‘Dutch Undesirable Nutrient and Food Score’ in the Zutphen Elderly Study. We assessed the association of these scores with 25 year CVD and all-cause mortality and life-years gained. We divided the men (age 65-84 years) into those with (n=210) and without (n=616) cardiovascular-metabolic diseases at baseline in 1985. During a median follow-up of 10.6 years (IQR 5.8-15.9) 806 participants died, of whom 359 from CVD. Diet scores did not predict death in all men. Among men with cardiovascular-metabolic diseases, ‘Dutch Healthy Nutrient and Food Score’ was associated with lower CVD (HR: 0.57; 95%CI: 0.35-0.93) and all-cause mortality risk (HR: 0.64; 95% CI: 0.44-0.94) comparing highest vs. lowest tertiles of the score. Men with cardiovascular-metabolic diseases in the highest vs. lowest tertile of the ‘Dutch Healthy Nutrient and Food Score’ lived 2.5 year longer. The ‘Dutch Healthy Nutrient and Food Score’ was not associated with CVD and all-cause mortality in men without cardiovascular-metabolic diseases. The ‘Dutch Undesirable Nutrient and Food Score’ was not associated with any of the outcomes.

In Chapter 8 we summarized the main findings of this thesis and reflected on some methodological considerations. First, we discussed the different approaches to derive dietary scores and patterns and the advantages and disadvantages of these methods. Second, we reflected on important aspects for creating a priori dietary scores and on further research. Finally, the general conclusions and implications were presented.

From the results presented in this thesis we conclude that adherence to a healthy diet is inversely associated with early stage markers of CVD (markers of endothelial function and oxidative stress), CVD and all-cause mortality. In summary, a healthy diet consists of plenty of vegetables and fruit, legumes, whole grains, nuts and seeds, moderate intake of fish/poultry/lean meats and low fat dairy, and limited intake of processed meats, refined grains, sugar sweetened beverages, ready meals and snacks. However, this thesis also showed that a high quality dietary pattern can be achieved in several different ways, and may differ among populations.

High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects
Esser, D. ; Dijk, S.J. van; Oosterink, E. ; Lopez, S. ; Muller, M.R. ; Afman, L.A. - \ 2015
Molecular Nutrition & Food Research 59 (2015)8. - ISSN 1613-4125 - p. 1563 - 1572.
triglyceride-rich lipoproteins - blood mononuclear-cells - men - atherosclerosis - inflammation - activation - receptors - adherence - profiles - alpha
Scope - Early perturbations in vascular health can be detected by imposing subjects to a high fat (HF) challenge and measure response capacity. Subtle responses can be determined by assessment of whole-genome transcriptional changes. We aimed to magnify differences in health by comparing gene-expression changes in peripheral blood mononuclear cells toward a high MUFA or saturated fatty acids (SFA) challenge between subjects with different cardiovascular disease risk profiles and to identify fatty acid specific gene-expression pathways. Methods and results -In a cross-over study, 17 lean and 15 obese men (50–70 years) received two 95 g fat shakes, high in SFAs or MUFAs. Peripheral blood mononuclear cell gene-expression profiles were assessed fasted and 4-h postprandially. Comparisons were made between groups and shakes. During fasting, 294 genes were significantly differently expressed between lean and obese. The challenge increased differences to 607 genes after SFA and 2516 genes after MUFA. In both groups, SFA decreased expression of cholesterol biosynthesis and uptake genes and increased cholesterol efflux genes. MUFA increased inflammatory genes and PPAR-a targets involved in ß-oxidation. Conclusion - Based upon gene-expression changes, we conclude that an HF challenge magnifies differences in health, especially after MUFA. Our findings also demonstrate how SFAs and MUFAs exert distinct effects on lipid handling pathways in immune cells.
Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men
Esser, D. ; Mars, M. ; Oosterink, E. ; Stalmach, A. ; Müller, M.R. ; Afman, L.A. - \ 2014
FASEB Journal 28 (2014)3. - ISSN 0892-6638 - p. 1464 - 1473.
flavanol-rich cocoa - endothelial function - mediated vasodilatation - cardiovascular health - postprandial lipemia - repeated exposure - metaanalysis - disease - atherosclerosis - prediction
Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45–70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (P
Macrophage Specific Caspase-1/11 Deficiency Protects against Cholesterol Crystallization and Hepatic Inflammation in Hyperlipidemic Mice
Hendrikx, T. ; Bieghs, V. ; Walenbergh, S.M.A. ; Gorp, P.J. van; Verheyen, F. ; Jeurissen, M.L.J. ; Steinbusch, M.M.F. ; Vaes, N. ; Binder, C.J. ; Koek, G.H. ; Stienstra, R. ; Netea, M.G. ; Hofker, M.H. ; Shiri-Sverdlov, R. - \ 2013
PLoS ONE 8 (2013)12. - ISSN 1932-6203 - 10 p.
nonalcoholic steatohepatitis - il-1-beta production - nlrp3 inflammasomes - nalp3 inflammasome - gut microbiota - autophagy - activation - atherosclerosis - crystals - disease
Background & Aims: While non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis combined with inflammation, the mechanisms triggering hepatic inflammation are unknown. In Ldlr(-/-) mice, we have previously shown that lysosomal cholesterol accumulation in Kupffer cells (KCs) correlates with hepatic inflammation and cholesterol crystallization. Previously, cholesterol crystals have been shown to induce the activation of inflammasomes. Inflammasomes are protein complexes that induce the processing and release of pro-inflammatory cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation is independent of caspase-11 in the canonical pathway of inflammasome activation, caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response to non-canonical inflammasome activators. So far, it has not been investigated whether inflammasome activation stimulates the formation of cholesterol crystals. We hypothesized that inflammasome activation in KCs stimulates cholesterol crystallization, thereby leading to hepatic inflammation. Methods: Ldlr(-/-) mice were transplanted (tp) with wild-type (Wt) or caspase-1/11(-/-) (dKO) bone marrow and fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 12 weeks. In vitro, bone marrow derived macrophages (BMDM) from wt or caspase-1/11(-/-) mice were incubated with oxLDL for 24h and autophagy was assessed. Results: In line with our hypothesis, caspase-1/11(-/-)-tp mice had less severe hepatic inflammation than Wt-tp animals, as evident from liver histology and gene expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11(-/-)-tp mice showed less cholesterol crystals, enhanced cholesterol efflux and increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy activity whereas BMDM from caspase-1/11(-/-) mice had normal autophagy activity. Conclusion: Altogether, these data suggest a vicious cycle whereby disturbed autophagy and decreased cholesterol efflux leads to newly formed cholesterol crystals and thereby maintain hepatic inflammation during NASH by further activating the inflammasome.
Effects of chocolate supplementation on metabolic and cardiovascular parameters in ApoE3L mice fed a high-cholesterol atherogenic diet
Yakala, G.K. ; Wielinga, P.Y. ; Suarez, M. ; Bunschoten, A. ; Golde, J.M. ; Arola, L. ; Keijer, J. ; Kleemann, R. ; Kooistra, T. ; Heeringa, P. - \ 2013
Molecular Nutrition & Food Research 57 (2013)11. - ISSN 1613-4125 - p. 2039 - 2048.
e-asterisk-3-leiden transgenic mice - coronary-heart-disease - kusanagi-hypercholesterolemic rabbits - reduce plasma-cholesterol - lipid-peroxidation - life-style - atherosclerosis - health - polyphenols - prevention
SCOPE: Dietary intake of cocoa and/or chocolate has been suggested to exhibit protective cardiovascular effects although this is still controversial. The aim of this study was to investigate the effects of chocolate supplementation on metabolic and cardiovascular parameters. METHODS AND RESULTS: Four groups of ApoE*3Leiden mice were exposed to the following diet regimens. Group 1: cholesterol-free control diet (CO). Group 2: high-dose (1.0% w/w) control cholesterol (CC). Group 3: CC supplemented chocolate A (CCA) and Group 4: CC supplemented chocolate B (CCB). Both chocolates differed in polyphenol and fiber content, CCA had a relatively high-polyphenol and low-fiber content compared to CCB. Mice fed a high-cholesterol diet showed increased plasma-cholesterol and developed atherosclerosis. Both chocolate treatments, particularly CCA, further increased plasma-cholesterol and increased atherosclerotic plaque formation. Moreover, compared to mice fed a high-cholesterol diet, both chocolate-treated groups displayed increased liver injury. Mice on high-cholesterol diet had elevated plasma levels of sVCAM-1, sE-selectin and SAA, which was further increased in the CCB group. Similar effects were observed for renal inflammation markers. CONCLUSION: The two chocolate preparations showed unfavorable, but different effects on cardiometabolic health in E3L mice, which dissimilarities may be related to differences in chocolate composition. We conclude that discrepancies reported on the effects of chocolate on cardiometabolic health may at least partly be due to differences in chocolate composition.
Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and electrochemiluminescense-based multi-array platform
Bussel, B.C.T. van; Ferreira, I. ; Waarenburg, M.P.H. ; Greevenbroek, M.M.J. van; Kallen, C.J.H. van der; Henry, R.M.A. ; Feskens, E.J.M. ; Stehouwer, C.D.A. ; Schalkwijk, C.G. - \ 2013
PLoS ONE 8 (2013)3. - ISSN 1932-6203 - 11 p.
coronary-artery-disease - public-health practice - low-grade inflammation - cardiovascular-disease - deming regression - atherosclerosis - risk - cytokines - markers - association
Background - In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. Methods - We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects’ cardiovascular risk factors by ANOVA. Results - Despite that both methods ranked individuals’ levels of biomarkers very similarly (Pearson’s r all=0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. Conclusions - Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.
Response to Ravnskov et al. on saturated fat and CHD
Pedersen, J.I. ; Norum, K.R. ; James, P.T. ; Brouwer, I.A. ; Katan, M.B. ; Clarke, R. ; Elmadfa, I. ; Kris-Etherton, P.M. ; Kromhout, D. ; Margetts, B.M. ; Mensink, R.P. ; Rayner, M. ; Uusitupa, M. - \ 2012
The British journal of nutrition 107 (2012)3. - ISSN 0007-1145 - p. 458 - 460.
heart-disease - cholesterol - atherosclerosis - hypothesis - mortality - statins
Low Serum Glutathione Peroxidase Activity Is Associated with Increased Cardiovascular Mortality in Individuals with Low HDLc’s
Buijsse, B. ; Lee, D.H. ; Steffen, L. ; Erickson, R.R. ; Luepker, R.V. ; Jacobs, D.R. ; Holtzman, J.L. - \ 2012
PLoS ONE 7 (2012)6. - ISSN 1932-6203
minnesota-heart-survey - low-density-lipoprotein - human-plasma - lipid peroxides - risk-factors - disease - cholesterol - trends - atherosclerosis - purification
Background Since oxidized LDL is thought to initiate atherosclerosis and the serum glutathione peroxidase (GPx3) reduces oxidized lipids, we investigated whether high GPx3 activity reduces cardiovascular disease (CVD) mortality. Methods We determined GPx3 in stored samples from the Minnesota Heart Survey of 130 participants who after 5 to 12 years of follow-up had died of CVD and 240 controls. Participants were 26 to 85 years old and predominantly white. In a nested case-control, study we performed logistic regressions to calculate odds ratios (OR) adjusted for age, sex, baseline year, body mass index, smoking, alcohol intake, physical activity, total and HDL cholesterols, systolic blood pressure, serum glucose and gamma glutamyltransferase (GTT) activity. The referent was the quartile with the highest GPx3 activity (quartile 4). Results OR’s for CVD mortality for increasing quartiles of GPx3 were 2.37, 2.14, 1.83 and 1.00 (P for trend 0.02). This inverse correlation was confined to those with HDLc’s below the median (P for interaction, 0.006). The OR’s for increasing quartiles of GPx3 in this group were 6.08, 5.00, 3.64 and 1.00 (P for trend, 0.002). Conclusions Individuals with both low HDLc and GPx3 activity are at markedly increased risk for death from CVD.
Cardiovascular risk management of hypertension and hypercholestrolaemia in the Netherlands: from unifactorial to multifactorial approach
Dis, I. van; Geleijnse, J.M. ; Verschuren, W.M.M. ; Kromhout, D. - \ 2012
Netherlands Heart Journal 20 (2012)7-8. - ISSN 1568-5888 - p. 320 - 325.
coronary-heart-disease - clinical-practice - cholesterol concentrations - european guidelines - randomized-trials - serum-cholesterol - task-force - prevention - society - atherosclerosis
About 30 years ago, the first Dutch unifactorial guidelines on hypertension and hypercholesterolaemia were developed. These guidelines have been revised several times, often after publication of landmark studies on new generations of drugs. In 1978, cut-off points for pharmacological treatment of hypertension were based on diastolic blood pressure values =115 mmHg, and in 2000 they were lowered to >100 mmHg. From 1997 onwards, cut-off points for systolic blood pressure values >180 mmHg were introduced, which became leading. In 1987, cut-offs for hypercholesterolaemia of =8 mmol/l were set and from 2006 pharmacological treatment was based on a total/HDL cholesterol ratio >8. Around 2000, treatment decisions for hypertension and/or hypercholesterolaemia were no longer based on high levels of individual risk factors, but on a multifactorial approach based on total risk of cardiovascular diseases (CVD), determined by a risk function. In the 2006 multidisciplinary guideline on cardiovascular risk management, the Framingham risk tables were replaced by European SCORE risk charts. A cut-off point of 10% CVD mortality was set in the Netherlands. In 2011, this cut-off point changed to 20% fatal plus nonfatal CVD risk. Nowadays, ‘the lower the risk factors, the lower the absolute risk’ is the leading paradigm in CVD prevention.
Bioinformatics tools and database resources for systems genetics analysis in miceça short review and an evaluation of future needs
Durrant, M.C. ; Swertz, M.A. ; Alberts, R. ; Arends, D. ; Möller, S. ; Mott, R. ; Prins, J.C.P. ; Velde, K.J. van der; Jansen, R.C. ; Schughart, K. - \ 2012
Briefings in Bioinformatics 13 (2012)2. - ISSN 1467-5463 - p. 135 - 142.
quantitative trait loci - collaborative cross - powerful resource - complex - atherosclerosis - genomics - biology - genes - r/qtl - men
During a meeting of the SYSGENET working group ‘Bioinformatics’, currently available software tools and databases for systems genetics in mice were reviewed and the needs for future developments discussed. The group evaluated interoperability and performed initial feasibility studies. To aid future compatibility of software and exchange of already developed software modules, a strong recommendation was made by the group to integrate HAPPY and R/qtl analysis toolboxes, GeneNetwork and XGAP database platforms, and TIQS and xQTL processing platforms. R should be used as the principal computer language for QTL data analysis in all platforms and a ‘cloud’ should be used for software dissemination to the community. Furthermore, the working group recommended that all data models and software source code should be made visible in public repositories to allow a coordinated effort on the use of common data structures and file formats.
Systolic blood pressure predicts cardiovascular mortality in a farming but not in a fishing community : a 40-year follow-up of theJapanese cohorts of the Seven Countries study
Hirai, Y. ; Geleijnse, J.M. ; Adachi, H. ; Imaizumi, T. ; Kromhout, D. - \ 2011
Circulation Journal 75 (2011)8. - ISSN 1346-9843 - p. 1890 - 1896.
coronary-heart-disease - fatty-acids - serum - metaanalysis - consumption - cholesterol - stroke - risk - omega-3-fatty-acids - atherosclerosis
Background: Blood pressure (BP) is a strong determinant of cardiovascular diseases (CVD). The strength of this association in 2 Japanese communities with different intakes of fish was investigated. Methods and Results: The analysis was carried out in the Japanese cohorts of the Seven Countries Study (Tanushimaru and Ushibuka), which were followed for 40 years. We included 1,006 subjects for whom data on baseline BP and relevant potential confounders were available. Data were analysed using multivariable Cox proportional hazard models. In Tanushimaru men, the systolic BP level was strongly directly related to risk of stroke and CVD mortality, with hazard ratios (HR) of 4.42 (2.02-9.70) for stroke and 3.05 (1.73-3.25) for CVD for BP levels =140mmHg compared to
Combined effort of alcohol consumption and lifestyle behaviors on risk of type 2 diabetes
Joosten, M.M. ; Grobbee, D.E. ; A, D.L. van der; Verschuren, W.M. ; Hendriks, H.F.J. ; Beulens, J.W.J. - \ 2010
American Journal of Clinical Nutrition 91 (2010)6. - ISSN 0002-9165 - p. 1777 - 1783.
coronary-heart-disease - physical-activity questionnaire - food frequency questionnaire - postmenopausal women - insulin sensitivity - relative validity - mellitus - diet - atherosclerosis - reproducibility
ackground: It has been suggested that the inverse association between alcohol and type 2 diabetes could be explained by moderate drinkers’ healthier lifestyles. Objective: We studied whether moderate alcohol consumption is associated with a lower risk of type 2 diabetes in adults with combined low-risk lifestyle behaviors. Design: We prospectively examined 35,625 adults of the Dutch European Prospective Investigation into Cancer and Nutrition (EPIC-NL) cohort aged 20–70 y, who were free of diabetes, cardiovascular disease, and cancer at baseline (1993–1997). In addition to moderate alcohol consumption (women: 5.0–14.9 g/d; men: 5.0–29.9 g/d), we defined low-risk categories of 4 lifestyle behaviors: optimal weight [body mass index (in kg/m2)
Intake of fish and marine n-3 fatty acids in relation to coronary calcification: the Rotterdam Study
Heine-Bröring, R.C. ; Brouwer, I.A. ; Vliegenthart, P.R. ; Rooij, F.J.A. van; Hofman, A. ; Oudkerk, M. ; Witteman, J.C.M. ; Geleijnse, J.M. - \ 2010
American Journal of Clinical Nutrition 91 (2010)5. - ISSN 0002-9165 - p. 1317 - 1323.
artery calcium score - heart-disease - controlled-trial - cardiovascular-disease - computed-tomography - risk prediction - atherosclerosis - omega-3-fatty-acids - supplementation - metaanalysis
Background: Epidemiologic and experimental data suggest a cardioprotective effect of n–3 (omega-3) fatty acids from fish [eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)]. Objective: The objective was to examine the association of fish and EPA plus DHA intakes with coronary calcification in a general older population. Design: Diet was assessed between 1990 and 1993 by using a semiquantitative 170-item food-frequency questionnaire. Coronary calcification was assessed 7 y later by electron-beam computed tomography in 1570 asymptomatic cardiac subjects with complete dietary data (44% men, mean age of 64 y). Calcium scores according to Agatston's method were divided into 10 (no/minimal coronary calcification), 11–400 (mild/moderate calcification), and >400 (severe calcification). Prevalence ratios (PRs) for mild/moderate and severe calcification were obtained in categories of fish and EPA plus DHA intake. PRs were adjusted for age, sex, body mass index, diabetes mellitus, socioeconomic status, smoking, alcohol intake, physical activity, and dietary factors. Results: Subjects with a fish intake >19 g/d had a significantly lower prevalence of mild/moderate calcification (PR: 0.87; 95% CI: 0.78, 0.98; full model) than did subjects who consumed no fish. Subjects with a high fish intake also had a lower prevalence of severe calcification (PR: 0.88; 95% CI: 0.74, 1.04), which was borderline statistically significant. EPA plus DHA intake showed no significant associations (PR: 0.93 and 0.97, respectively; P > 0.05). Conclusions: We found a weak inverse association between fish intake and coronary calcification. If confirmed in other population-based studies, more research is warranted to determine which components in fish can inhibit vascular calcification.
Cardiovascular risk factors and dementia mortality: 40 years of follow-up in the Seven Countries Study
Alonso, A. ; Jacobs, D.R. ; Menotti, A. ; Nissinen, A. ; Dontas, A. ; Kafatos, A. ; Kromhout, D. - \ 2009
Journal of the Neurological Sciences 280 (2009)1-2. - ISSN 0022-510X - p. 79 - 83.
alzheimers-disease - vascular dementia - cognitive decline - blood-pressure - midlife - smoking - cholesterol - life - atherosclerosis - metaanalysis
Previous research shows that cardiovascular risk factors in mid-adulthood could increase the risk of dementia later in life, but studies with very long follow-up are still scarce. We assessed whether cardiovascular risk factors measured in midlife were associated with dementia mortality during a 40-year follow-up. 10,211 men, aged 40-59 at baseline, from 13 cohorts of the Seven Countries Study were followed for 40 years. Information on cardiovascular risk factors was obtained at baseline from questionnaires and a physical examination. Dementia death was assigned if there was any mention of dementia on the death certificate. Associations between cardiovascular risk factors and death from dementia were estimated through Cox proportional hazards models. We identified 160 dementia deaths during the follow-up. Smoking, hypercholesterolemia, high blood pressure, low forced vital capacity and previous history of cardiovascular disease at baseline were associated with a higher risk of death from dementia in the follow-up. The hazard ratio (HR) of dementia death among heavy smokers was 1.58 (95% confidence interval (CI) 1.03, 2.43) compared to non-smokers. Similarly, the HR (95% CI) among those with systolic BP -> 160 or diastolic BP -> 95 mm Hg compared to normotensives (<140/90) was 1.55 (1.02, 2.35). Individuals with the largest forced vital capacity had a lower risk of dying of dementia (HR 0.54, 95% CI 0.30, 0.98). Finally, total serum cholesterol was directly associated with higher risk of dementia mortality (p for trend = 0.03). In men, cardiovascular risk factors in midlife are associated with increased risk of dementia death later in life
The increase of fatty acid-binding protein aP2 in overweight and obese children: interactions with dietary fat and impact on measures of subclinical inflammation
Aeberli, I. ; Beljean, N. ; Lehmann, R. ; I'Allemand, D. ; Spinas, G.A. ; Zimmermann, M.B. - \ 2008
International Journal of Obesity 32 (2008)10. - ISSN 0307-0565 - p. 1513 - 1520.
human thp-1 macrophages - for-disease-control - metabolic syndrome - insulin-resistance - lipid-metabolism - swiss children - atherosclerosis - glucose - prevention - expression
In adults, circulating aP2 may link obesity, inflammation and the metabolic syndrome, but there are few data in children. Experimental models support that dietary factors, particularly dietary fat, may be major determinants of phenotype. OBJECTIVE: The aim of this study was to investigate, in normal, overweight and obese children, the relationships among aP2, the metabolic syndrome, inflammation and diet. DESIGN: This was a cross-sectional study conducted in Northern Switzerland. SUBJECTS: Subjects for this study were 6- to 14-year-old, prepubertal and early pubertal, normal weight, overweight and obese children (n=124). MAIN OUTCOME MEASURES: Body mass index (BMI), body fat percent, waist-to-hip ratio, blood pressure, circulating aP2, fasting insulin, C-reactive protein (CRP), plasma lipids and dietary intakes of macro- and micronutrients were determined. RESULTS: Circulating aP2 markedly increased with increasing central and total adiposity, and predicted measures of insulin resistance. Independent of BMI standard deviation scores and puberty, aP2 correlated with intake of the antioxidant vitamins A, C and E as well as circulating concentrations of CRP, leptin and low-density lipoprotein cholesterol. Children with lower aP2 concentrations consuming high-fat diets did not show an increase in fasting insulin or CRP, whereas those with higher aP2 concentrations showed marked increases in these measures with high intakes of fat or saturated fat. CONCLUSIONS: Increased central and overall adiposity in children are associated with higher circulating aP2 concentrations. In children with high dietary intakes of total fat and saturated fat, but not those with low intakes, higher aP2 concentrations are associated with measures of insulin resistance and inflammation.
Blood donation, body iron status and carotid intima-media thickness
Engberink, M.F. ; Geleijnse, J.M. ; Durga, J. ; Swinkels, D.W. ; Kort, W.L.A.M. de; Schouten, E.G. ; Verhoef, P. - \ 2008
Atherosclerosis 196 (2008)2. - ISSN 0021-9150 - p. 856 - 862.
transferrin-bound iron - coronary-heart-disease - acute myocardial-infarction - eastern finnish men - serum ferritin - risk - stores - atherosclerosis - association - hemochromatosis
Iron could promote free radical formation, which may lead to injury of the arterial wall and atherosclerosis. Blood donation may reduce cardiovascular risk by lowering body iron status. We collected data on blood donation history and intima-media thickness of the common carotid artery (CIMT) in 819 subjects (50-70 years), who were recruited from municipal and blood bank registries in The Netherlands. Serum iron parameters were assessed, including non-transferrin bound iron (NTBI) that has recently been found in conditions of iron overload. Serum ferritin was lower in current donors (n=443; 44mug/L) than in ex-donors (n=120; 114mug/L) and never-donors (n=256; 124mug/L, P for trend /=49 times during life or >/=2 times per year), although not statistically significant. CIMT was not significantly related to NTBI. Frequent blood donation, resulting in lowered body iron, might give some protection against accelerated atherosclerosis.
Fasting induces changes in peripheral blood mononuclear cell gene expression profiles realted to increases in fatty acid ß-oxidation: functional role of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells 1-3
Bouwens, M. ; Afman, L.A. ; Müller, M.R. - \ 2007
American Journal of Clinical Nutrition 86 (2007)5. - ISSN 0002-9165 - p. 1515 - 1523.
pyruvate-dehydrogenase complex - human skeletal-muscle - ppar-alpha - metabolic genes - rna expression - t-lymphocytes - starvation - atherosclerosis - gamma - eicosanoids
Background: Peripheral blood mononuclear cells (PBMCs) are the only readily available cells in healthy humans. Various studies showed disease-characteristic gene expression patterns in PBMCs. However, little is known of nutritional effects on PBMC gene expression patterns. Fatty acids are nutrients that regulate gene expression by activating the nuclear receptor peroxisome proliferator¿activated receptor (PPAR). PBMCs express PPAR, making these cells interesting to study FA-dependent gene expression. Objective: The aim of this study was to elucidate whether PBMC gene expression profiles also reflect nutrition-related metabolic changes. Furthermore, we focused on the specific role of PPAR in regulation of PBMC gene expression during fasting, when plasma free fatty acids are elevated. Design: Four healthy male volunteers fasted for 48 h. PBMC RNA was hybridized on Affymetrix whole genome microarrays. To elucidate the role of PPAR, PBMCs of 9 blood donors were incubated with the specific PPAR ligand Wy14643. Results: After 24 and 48 h of fasting, 1200 and 1386 genes were changed >1.4-fold, respectively. Many of those genes were involved in fatty acid ß-oxidation and are known PPAR target genes. Incubation of PBMCs with Wy14643 resulted in up-regulation of genes that were also up-regulated during fasting. Conclusions: We conclude that PBMC gene expression profiles reflect nutrition-related metabolic changes such as fasting and that part of the fasting-induced changes are likely regulated by PPAR.
Proteomic biomarkers of peripheral blood mononuclear cells obtained from postmenopausal women undergoing an intervention with soy isoflavones
Fuchs, D. ; Vafeiadou, K. ; Hall, W.L. ; Daniel, H. ; Williams, C.M. ; Schroot, J.H. ; Wenzel, U. - \ 2007
American Journal of Clinical Nutrition 86 (2007)5. - ISSN 0002-9165 - p. 1369 - 1375.
nadp(+)-dependent isocitrate dehydrogenase - hormone replacement therapy - plasma total homocysteine - cardiovascular-disease - equol-production - endothelial function - enriched foods - protein - risk - atherosclerosis
Background: The incidence of cardiovascular diseases increases after menopause, and soy consumption is suggested to inhibit disease development. Objective: The objective was to identify biomarkers of response to a dietary supplementation with an isoflavone extract in postmenopausal women by proteome analysis of peripheral blood mononuclear cells. Design: The study with healthy postmenopausal woman was performed in a placebo-controlled sequential design. Peripheral mononuclear blood cells were collected from 10 volunteers after 8 wk of receiving daily 2 placebo cereal bars and after a subsequent 8 wk of intervention with 2 cereal bars each providing 25 mg of isoflavones. The proteome of the cells was visualized after 2-dimensional gel electrophoresis, and peptide mass fingerprinting served to identify proteins that by the intervention displayed altered protein concentrations. Results: Twenty-nine proteins were identified that showed significantly altered expression in the mononuclear blood cells under the soy-isoflavone intervention, including a variety of proteins involved in an antiinflammatory response. Heat shock protein 70 or a lymphocyte-specific protein phosphatase and proteins that promote increased fibrinolysis, such as -enolase, were found at increased intensities, whereas those that mediate adhesion, migration, and proliferation of vascular smooth muscle cells, such as galectin-1, were found at reduced intensities after soy extract consumption. Conclusion: Proteome analysis identified in vivo markers that respond to a dietary intervention with isoflavone-enriched soy extract in postmenopausal women. The nature of the proteins identified suggests that soy isoflavones may increase the antiinflammatory response in blood mononuclear cells that might contribute to the atherosclerosis-preventive activities of a soy-rich diet.
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