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Abstract Background Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. Some in vitro experiments have previously suggested that high-density lipoprotein (HDL) co-incubated with LDL prevents Cu2+-induced oxidation of LDL, while some other studies have observed an opposite effect. To comprehensively clarify the role of HDL in this context, we isolated LDL, HDL2 and HDL3 from sera of 61 free-living individuals (33 women and 28 men). Results When the isolated LDL was subjected to Cu2+-induced oxidation, both HDL2 and HDL3 particles increased the rate of appearance and the final concentration of conjugated dienes similarly in both genders. Oxidation rate was positively associated with polyunsaturated fatty acid content of the lipoproteins in that it was positively related to the content of linoleate and negatively related to oleate. More saturated fats thus protected the lipoproteins from damage. Conclusion We conclude that in vitro HDL does not protect LDL from oxidation, but is in fact oxidized fastest of all lipoproteins due to its fatty acid composition, which is oxidation promoting.

The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids. [ABSTRACT FROM PUBLISHER]

Abstract Background Wartime stress has been associated with increased late-life mortality of all causes of death. We evaluated whether wounded Finnish World War II veterans who were alive at the age of 55 have increased long-term coronary heart disease (CHD) mortality. Methods Health survey data were recorded in 1980 from 667 men, aged 55 years. Of them 102 had been wounded or injured in action during 1939-1945. The remaining participants served as the comparison group. The death certificates during a 28-year follow-up were obtained from the national statistics centre. Statistical comparisons were done by Cox proportional hazard regression model. Results There were altogether 140 deaths from CHD. In men who had been wounded or injured in action the crude CHD mortality rate per 10,000 population was 2843, while in the comparison group the corresponding figure was 1961. Men who had been wounded or injured in action were 1.7 times (95% CI 1.1-2.5; p = 0.01) more likely to die from CHD than the comparison group. Conclusions Physical trauma at young adulthood may extend to lifelong effects on health. This study suggests that being physically wounded or injured in war may lead to increased CHD mortality in late adulthood in a Finnish population.

Abstract Background Dietary fatty acids may modulate inflammation in macrophages of the atherosclerotic plaque, affecting its stability. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) generally promotes inflammation, while the PUFAs of the n-3 series eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are considered anti-inflammatory. We determined how these PUFAs influence MMP-9 expression and secretion by the human monocytic cell line (MonoMac 6) at baseline and after 24-hour exposure. MMP-9 protein was measured by zymography and relative levels of MMP-9 mRNA were determined using quantitative real time PCR. Results Supplementation with AA (but not the n-3 fatty acids) increased, in a dose-dependent manner, expression of MMP-9 protein. This stimulation was regulated at the mRNA level. MMP-9 secretion started after 1 h of incubation and could not be prevented by simultaneous presence of n-3 series fatty acids. Finally, the secretion could be attenuated by LY 294002, a specific phosphatidylinositol-3-kinase (PI3K) inhibitor and by SH-5, a selective Akt inhibitor, suggesting that activation of PI3K by AA leads to augmented and sustained MMP-9 production. Conclusion This study shows that of the PUFA studied, AA alone influences the expression of MMP-9, which might have implications in MMP-9 induced plaque rupture.

Abstract Background Polyunsaturated fatty acids (PUFA) are thought to play important roles in inflammation. The n-3 series is considered as anti-inflammatory, and some studies have reported increased plasma n-3 polyunsaturated fatty acid pattern in chronic inflammatory conditions. In this study we sought to clarify relationships of the levels of arachidonic acid and the polyunsaturated n-3 fatty acid compositions of isolated LDL, HDL2 and HDL3 particles with matrix metalloproteinase-9 (MMP-9), a marker of inflammation. Results The subjects were divided into two groups: those with lower and those with higher than the median serum MMP-9 concentration. In all lipoprotein fractions, the mean percentage of docosapentaenoic acid (C22:5n-3) was higher in the group of subjects with higher MMP-9 level than in those with lower serum MMP-9 concentration (P < 0.01 for all). Likewise, the ratio of docosapentaenoic acid to arachidonic acid (C20:4n-6) was higher in the subjects with higher MMP-9 compared with the lower MMP-9 group (P < 0.001 for all). Conclusion So far, the evidence for an anti-inflammatory role of the n-3 PUFA has come from dietary interventions. Our results were obtained from a free-living population and indicate that there is a positive correlation between n-3 docosapentaenoic acid and MMP-9. What had triggered the rise in MMP-9 is not known, since serum level of MMP-9 is raised in many inflammatory conditions. These findings may indicate an increased biosynthesis of n-3 polyunsaturated fatty acids in subclinical inflammation.

Logistics and supply chain management are critical for economic sustainability. In this research, we aim to identify the most critical factors to logistics and supply chain performance for a small open economy by reporting survey results from Estonian manufacturing, trading and logistics service companies. By comparing survey results from 2012 and 2018, we also analyze how these critical factors may have changed during the last years. In the survey, the significance of competitiveness, functionality of logistics, and information and communication technologies (ICT) among others were included. The results indicate that the importance of factors such as purchasing, demand forecasting and operations planning have increased. Overall, purchasing and demand forecasting are considered more important than other factors. Surprisingly, logistics was considered less vital in 2018 than in 2012. Most of the current challenges in companies arise from demand management (forecasting and planning), increasing labour costs and regulatory changes. On ICT side change has been from traditional communications more towards digital, and especially using specific platforms (portals, intranet/extranet)., (© 2020 The Author(s). Published by Elsevier B.V.)

Background: We examined the association of three known genome-wide association study loci for blood lipids that have lead traits for triglycerides with hypertension in the Tampere adult population cardiovascular risk study., Methods: A Finnish cohort of 190 men with diagnosed hypertension and 279 controls were analyzed. Samples were genotyped for low-density lipoprotein receptor-related protein 1 rs11613352 (C>T), angiopoietin-like 3 rs2131925 (T>G), and fatty acid desaturase 1 rs174546 (C>T) polymorphisms using competitive allele-specific polymerase chain reaction technique., Results: At the age of 50, subjects with low-density lipoprotein receptor-related protein 1 rs11613352 (C>T) minor genotype TT had significantly more hypertension than those with the C allele (OR 5.17, CI 2.03-12.74, p < 0.001). Subjects with angiopoietin-like 3 rs2131925 (T>G) T allele had more hypertension than those with the minor genotype GG (OR 5.02, CI 1.40-17.98, p = 0.013). Fatty acid desaturase 1 rs174546 (C>T) did not associate with hypertension., Conclusion: Association of low-density lipoprotein receptor-related protein 1 rs11613352 and angiopoietin-like 3 rs2131925 with hypertension might imply a direct effect at the artery wall., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Cell surface heparan sulfate (HS) proteoglycans interact with other extracellular matrix (ECM) components, and HS-binding regions are present in ECM proteins such as fibronectin and fibrillin. Because of their previously established role in susceptibility to intracranial aneurysms, the authors sought to determine whether polymorphisms of fibronectin (FN1, rs2289202) and fibrillin 2 (FBN2, rs331069) associate with selected cardiovascular risk factors and events in the TAMRISK study. A 50-year-old Finnish cohort of 810 subjects of whom 340 had diagnosed hypertension was analyzed. Samples were genotyped for FN1 rs2289202 and FBN2 rs331069 polymorphisms. Incidence of myocardial infarction (I21-I22), transient cerebral ischemic attacks (TIA, G45) and cerebrovascular diseases (I60-I69) were followed up until the subjects were on the average 60 years old. Subjects with FN1 rs2289202 (G>A) minor genotype AA had significantly more cerebrovascular disease than those with the G allele [P<0.001, odds ratio (OR), 8.73; confidence index (CI), 2.79-27.31], although those with the A allele had lower body mass index (P=0.008). Subjects with fibrillin rs331069 (T>C) minor genotype CC had more atherothrombotic disease (P=0.012, OR, 3.16; CI, 1.29-7.71), as measured by combined myocardial infarction and TIA, than those with the T allele. The gene polymorphisms for fibronectin and fibrillin 2 appear to associate with vascular disease.

Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed. Samples were genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using competitive allele-specific PCR (KASP) technique. Prevalence of ischemic heart diseases (I20-I25) and incidence of cerebrovascular diseases (I60-I69) and transient cerebral ischemic attacks (TIA) (G45) were followed up until the subjects were on the average 60 years old. GLCE rs3865014 G allele showed negative association with hypertension (p = 0.022), waist circumference (p = 0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029), low-density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular events (p = 0.011). SULF2 rs2281279 showed no association with the studied parameters. The GLCE gene polymorphism rs3865014 appears to have biological relevance in human pathophysiology., (© 2016 John Wiley & Sons Ltd/University College London.)

Background: Decorin is an extracellular matrix proteoglycan that may attenuate progression of atherosclerosis and its complications, such as stroke. Among its multitude of functions, decorin has been suggested to serve as a receptor for resistin, an adipokine involved in energy homeostasis. The GG genotype of the decorin polymorphism rs7308752 (A>G) and the CC genotype of the rs516115 (T>C) are associated with decreased plasma resistin levels., Aims: The association of the above decorin genotypes with selected cardiometabolic risk factors and cerebrovascular events was studied in the Tampere adult population cardiovascular risk (TAMRISK) study., Materials and Methods: A Finnish cohort of 336 subjects with diagnosed hypertension and 444 controls was analyzed. Samples were genotyped for decorin rs7308752 and rs516115 polymorphisms using a Competitive Allele-Specific PCR (KASP) technique. Cerebrovascular diseases (I60-I69), including transient cerebral ischemic attacks (G45), were followed up from 2005 to 2014., Results: Subjects with either of decorin rs7308752 genotypes AG/GG had higher serum glucose (p = 0.015) and higher heart rate (p = 0.017) than those with AA genotype. Similarly, decorin rs516115 genotypes TC/CC were associated with higher serum glucose (p = 0.034) and higher frequency of cerebrovascular diseases (p = 0.015) compared to the TT genotype. However, decorin polymorphisms were not associated with hypertension or body mass index., Conclusions: These two decorin polymorphisms appear to have biological relevance in human vascular pathophysiology.

Background: Human fatty acid transporter CD36 gene variations have previously been associated with fat preferences and obesity. These variations could thus cause overweight and hypothetically lead to hypertension. The association of CD36 SNP rs1761667 with body mass index (BMI) and hypertension was therefore studied in a Finnish cohort of adults., Methods: The data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). A total of 314 cases with diagnosed hypertension, and 422 non-hypertensive healthy controls were selected from a Finnish periodic 50-year-old health examination cohort. Most subjects had prior health examination data also from their 40- and 45-year examinations. DNA was extracted from buccal swabs and the human CD36 genetic variant was analyzed using KASP genotyping., Results: The CD36 SNP rs1761667 variant AA was significantly associated with lower BMI, as compared to variants AG and GG at the ages of 40-, 45-, and 50 years (p < 0.001, p = 0.005 and p = 0.013, respectively). No association of this CD36 variation with hypertension was found., Conclusions: CD36 rs1761667 was associated with BMI in the TAMRISK study. Considering the multitude of roles of CD36 in processes related to fatty acid metabolism and sensing in the body, it is plausible that genetic variation in human fatty acid transporter CD36 can have effects on regulation of energy homeostasis.

Background: Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. We have previously shown that HDL does not protect LDL from oxidation in vitro, but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA status. There is a deletion [T/-] in the promoter region of the Δ6 -desaturase gene (FADS2, rs 3834458), which has a direct inhibitory influence on production of PUFA from linoleic and alpha-linolenic acid. To investigate the possible role of rs 3834458 in lipoprotein modification, oxidation of LDL with HDL₂ or HDL₃ were analyzed from plasma of 58 free-living individuals., Results: Total eicosapentaenoic acid and arachidonic acid were significantly decreased in plasma from the 10 subjects homozygous for the deletion in FADS2 rs 3834458. When the isolated LDL and HDL₂ were subjected to Cu²⁺-induced oxidation, these subjects showed decreased rate of appearance (p = 0.027) and the final concentration of conjugated dienes (p = 0.033) compared to the other genotypes. For oxidation of LDL with HDL₃, the final concentration of conjugated dienes was also significantly decreased in subjects with [-/-] compared with [T/T] and [T/-] (p = 0.034)., Conclusion: We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins.

Objective: Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values., Methods: ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT)., Results: Correlations between estimated and measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1-ratio (both measured and estimated) associated with cIMT in multivariable models, and predicted cIMT at all levels of LDL-cholesterol concentration. Strong correlations between the estimated apolipoproteins and those measured from fasting samples were replicated in over 15,000 Caucasian subjects (r = 0.93-0.96 for apoB and r = 0.91-0.92 for apoA1). Correlations with cIMT were replicated in over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting lipids in over 20,000 individuals in the INTERHEART study was better than any of the cholesterol measures for estimation of the myocardial risk., Conclusions: Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute clinically useful estimates of apoB and apoA1. Using this methodology, estimates of apolipoproteins could be routinely added to laboratory reports to complement lipoprotein lipids in risk assessment., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients were studied. Furthermore, 34 clones representing 21 bacterial sequence-types from the reagents used for DNA extraction and PCR amplification were determined. After subtraction of these potential methodological contaminants, 23 bacterial sequence-types were considered as clinically relevant findings. The most prominent phylum, Actinobacteria, accounted for 74% of these relevant sequences. Furthermore, according to the Human Microbiome project database, interestingly, nearly all (94%) of the sequences were associated with the human skin microbiome.

Cholesterol-lowering treatment has been suggested to delay progression of prostate cancer by decreasing serum LDL. We studied in vitro the effect of extracellular LDL-cholesterol on the number of prostate epithelial cells and on the expression of key regulators of cholesterol metabolism. Two normal prostatic epithelial cell lines (P96E, P97E), two in vitro immortalized epithelial cell lines (PWR-1E, RWPE-1) and two cancer cell lines (LNCaP and VCaP) were grown in cholesterol-deficient conditions. Cells were treated with 1-50 µg/ml LDL-cholesterol and/or 100 nM simvastatin for seven days. Cell number relative to control was measured with crystal violet staining. Changes in mRNA and protein expression of key effectors in cholesterol metabolism (HMGCR, LDLR, SREBP2 and ABCA1) were measured with RT-PCR and immunoblotting, respectively. LDL increased the relative cell number of prostate cancer cell lines, but reduced the number of normal epithelial cells at high concentrations. Treatment with cholesterol-lowering simvastatin induced up to 90% reduction in relative cell number of normal cell lines but a 15-20% reduction in relative number of cancer cells, an effect accompanied by sharp upregulation of HMGCR and LDLR. These effects were prevented by LDL. Compared to the normal cells, prostate cancer cells showed high expression of cholesterol-producing HMGCR but failed to express the major cholesterol exporter ABCA1. LDL increased relative cell number of cancer cell lines, and these cells were less vulnerable than normal cells to cholesterol-lowering simvastatin treatment. Our study supports the importance of LDL for prostate cancer cells, and suggests that cholesterol metabolism in prostate cancer has been reprogrammed to increased production in order to support rapid cell growth.

Background/aims: Hyperlipidemia is one known etiology of acute pancreatitis. Alcohol use is known to induce changes in lipid metabolism and might alter the serum lipid and fatty acid profile. We hypothesized that these changes may explain individual susceptibility of developing acute pancreatitis. We compared lipid and fatty acid profiles of patients with acute alcoholic pancreatitis and alcoholic controls., Methods: 19 patients with their first alcoholic pancreatitis and 20 controls were included. Late follow-up samples were obtained from 16 patients. Serum lipids were analyzed enzymatically and the fatty acid profile using gas chromatography., Results: The concentrations of serum total cholesterol, LDL-cholesterol and HDL-cholesterol were markedly lower in patients than in controls during the acute disease but normalized after follow-up. Patients had statistically significantly lower fatty acid proportions of saturated C14:0, polyunsaturated C18:2, C18:3 and C20:3 of the n-6-series and C18:3 of the n-3-series than controls. In contrast, patients had higher percentages of saturated C16:0 and monounsaturated C18:1n9 fatty acids than controls. Mead acid, C20:3n9, marker of essential fatty acid deficiency, was lower in patients than in controls. C14:0, C20:3n6, C18:3n3 and C20:3n9 remained altered after follow-up., Conclusion: Serum lipid and fatty acid levels were significantly altered during the acute disease and returned toward normal after 18-24 months, suggesting that the changes are secondary to acute pancreatitis. They are unlikely to be the much sought 'trigger factor' of pancreatic necro-inflammation. However, further studies are warranted to fully establish this point., (Copyright © 2012. Published by Elsevier B.V.)

Epidemiological studies have linked statin use with a decreased risk of advanced prostate cancer and an improved recurrence-free survival after radical therapy. It is unclear, however, whether statins could have direct effects against prostate cancer in a clinical setting, as their growth-inhibiting effects on prostate cancer cells have been demonstrated at drug concentrations which exceed the level in plasma during standard clinical dosing. We compared responses to high-dose and therapeutic-dose simvastatin in normal and cancerous prostate epithelial cells. Simvastatin was more effective at inhibiting the growth of normal prostate epithelial cells than of cancer cells. At therapeutic 100 nM concentration simvastatin had a cytostatic effect on normal cells: apoptosis was only slightly induced, but a decrease in cell cycle activity and an increase in senescence were observed. At therapeutic concentrations, lipophilic simvastatin caused a stronger growth inhibition than did hydrophilic rosuvastatin. In contrast, 10 μM simvastatin had a cytotoxic effect both on normal and cancer cells. Addition of LDL-cholesterol effectively reversed the cytostatic effect in all cell lines, but overcoming the cytotoxicity of 10 μM simvastatin required a combination of LDL-cholesterol and mevalonate. As LDL-cholesterol completely prevented the growth-inhibiting effect of therapeutic-dose simvastatin already at low, subphysiological concentrations it is unlikely that statins have direct effects on growth of prostate epithelial cells in vivo. Statins' possible benefits against prostate cancer could be due to systemic cholesterol-lowering, as suggested by epidemiological studies. Future clinical studies evaluating the effects of statins on prostate cancer prevention should monitor serum LDL and should probably administer statins at higher concentrations than those currently used in the treatment of hypercholesterolemia., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Irritable bowel syndrome (IBS) is a fluctuating disorder of the gastrointestinal tract, characterized by abdominal pain and change in bowel habit. We wanted to investigate subjects with IBS for signs of disturbed intestinal absorption of fatty acids, as reflected in serum composition., Material and Methods: Serum samples were obtained from 32 adults with IBS, and from 59 controls. Serum fatty acids were analyzed by capillary gas-liquid chromatography., Results: Especially the proportions of arachidonic acid (20:4 n-6) and the long-chain polyunsaturated fatty acids of the n-3 family docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) were decreased in subjects with IBS. The proportions of unsaturated and monounsaturated fatty acids were generally increased in IBS compared to controls., Conclusions: Although organic disease has been ruled out in patients with IBS, they presented signs of inadequate supply of long-chain fatty acids. Supplementation with n-3 fatty acids may be implicated.