Association of low-density lipoprotein receptor-related protein 1 rs11613352 and angiopoietin-like 3 rs2131925 with hypertension in men-the Tampere adult population cardiovascular risk study.

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.

Gene polymorphisms of fibronectin rs2289202 and fibrillin 2 rs331069 associate with vascular disease, the TAMRISK study.

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.

Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI, Blood Hemoglobin, Hypertension, and Cerebrovascular Events, the TAMRISK Study.

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.

Decorin Genotypes, Serum Glucose, Heart Rate, and Cerebrovascular Events: The Tampere Adult Population Cardiovascular Risk Study.

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.

Contribution of fatty acid transporter (CD36) genetic variant rs1761667 to body mass index, the TAMRISK study.

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.

Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro.

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 Cu²âº-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.

Bacterial DNA signatures in carotid atherosclerosis represent both commensals and pathogens of skin origin.

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.

Computationally estimated apolipoproteins B and A1 in predicting cardiovascular risk.

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.

The importance of LDL and cholesterol metabolism for prostate epithelial cell growth.

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.

Serum lipid and fatty acid profiles are highly changed in patients with alcohol induced acute pancreatitis.

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.

Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL.

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.

Late-life coronary heart disease mortality of Finnish war veterans in the TAMRISK study, a 28-year follow-up.

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.

Serum fatty acid profile in subjects with irritable bowel syndrome.

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.

Serum cholesterol and expression of ApoAI, LXRbeta and SREBP2 in vitamin D receptor knock-out mice.

Vitamin D insufficiency has been reported to be associated with increased blood cholesterol concentrations. Here we used two strains of VDR knock-out (VDR-KO) mice to study whether a lack of vitamin D action has any effect on cholesterol metabolism. In 129S1 mice, both in male and female VDR-KO mice serum total cholesterol levels were significantly higher than those in wild type (WT) mice (20.7% (P=0.05) and 22.2% (P=0.03), respectively). In addition, the serum high-density lipoprotein-bound cholesterol (HDL-C) level was 22% (P=0.03), respectively higher in male VDR-KO mice than in WT mice. The mRNA expression levels of five cholesterol metabolism related genes in livers of 129S1 mice were studied using quantitative real-time PCR (QRT-PCR): ATP-binding cassette transporter A1 (ABCA1), regulatory element binding protein (SREBP2), apolipoprotein A-I (ApoAI), low-density lipoprotein receptor (LDLR) and liver X receptor beta (LXRbeta). In the mutant male mice, the mRNA level of ApoAI and LXRbeta were 49.2% (P=0.005) and 38.8% (P=0.034) higher than in the WT mice. These changes were not observed in mutant female mice, but the female mutant mice showed 52.5% (P=0.006) decrease of SREBP2 mRNA expression compared to WT mice. Because the mutant mice were fed with a special rescue diet, we wanted to test whether the increased cholesterol levels in mutant mice were due to the diet. Both the WT and mutant NMRI mice were given the same diet for 3 weeks before the blood sampling. No difference in cholesterol or in HDL-C between WT and mutant mice was found. The results suggest that the food, gender and genetic background have an effect on the cholesterol metabolism. Although VDR seems to regulate some of the genes involved in cholesterol metabolism, its role in the regulation of serum cholesterol seems to be minimal.

Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.

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.

Serum fatty acid profile in celiac disease patients before and after a gluten-free diet.

OBJECTIVE: Celiac disease (CD) is characterized by villous atrophy with crypt hyperplasia and inflammation of the small intestinal mucosa leading to disturbed epithelial transport. In untreated CD, fat malabsorption can occur. The aim of this study was to investigate the profile of serum fatty acids in newly detected CD before and after treatment with a gluten-free diet. MATERIAL AND METHODS: Serum samples were obtained from 50 adults with active CD showing small-bowel mucosal villous atrophy, from the same patients in remission after treatment with a gluten-free diet, 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 active CD. Serum levels of these fatty acids increased during remission, but still remained significantly lower than control values. Levels of unsaturated and monounsaturated fatty acids were generally increased in subjects with CD compared with those in controls. CONCLUSIONS: In patients with CD, determination of serum fatty acid composition can be considered if the dietary history or symptoms suggest an inadequate supply of long-chain fatty acids.

Childhood levels of serum apolipoproteins B and A-I predict carotid intima-media thickness and brachial endothelial function in adulthood: the cardiovascular risk in young Finns study.

OBJECTIVES: The aim of this study was to determine whether apolipoproteins (apo) B and A-I measured in childhood and adolescence predict atherosclerosis in adulthood. BACKGROUND: Exposure to dyslipidemia in childhood predicts the development of atherosclerosis. Apolipoproteins B and A-I might be good markers of atherogenic dyslipidemia, but there is a paucity of information concerning their importance in childhood. METHODS: Apolipoproteins B and A-I, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure, obesity, insulin, C-reactive protein, and smoking were assessed in 1980 and 2001 among 879 subjects in the Cardiovascular Risk in Young Finns Study (ages 3 to 18 years at baseline). Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured in 2001 at the age of 24 to 39 years. RESULTS: In subjects ages 12 to 18 years at baseline, apoB and apoB/apoA-I ratio were directly (p < 0.001) related and apoA-I was inversely (p = 0.01) related with adulthood IMT. In subjects ages 3 to 18 years at baseline, apoB (p = 0.02) and the apoB/apoA-I ratio (p < 0.001) were inversely related and apoA-I (p = 0.003) was directly related to adulthood FMD. These relations were not altered when the effects of nonlipid risk factors and adulthood apolipoproteins were taken into account. The apoB/apoA-I ratio measured in adolescence was superior to LDL/HDL ratio (c-values, 0.623 vs. 0.569, p = 0.03) in predicting increased IMT in adulthood (IMT >or=90th percentile and/or carotid plaque). CONCLUSIONS: Apolipoproteins B and A-I measured in children and adolescents reflect a lipoprotein profile predisposing to the development of subclinical atherosclerosis in adulthood. These markers might have value in pediatric lipid risk assessment.

Diet does not explain the high prevalence of dyslipidaemia in paediatric renal transplant recipients.

Dyslipidaemia exists frequently after renal transplantation (RTx) and promotes atherosclerosis. In this study, we examined the association between daily intake of nutrients and serum lipids after paediatric RTx. We studied 45 children with acceptably functioning kidney grafts and adequately completed food records at a median age of 10.6 years (range 4.3-17.2 years), a median 5.2 years (range 1.0-11.0) after RTx, and 178 healthy controls at a median age of 9.0 years (range 3.2-18.7 years). Serum total cholesterol (TC), triglyceride, and apolipoprotein B concentrations were higher in the RTx patients than in the controls (P < 0.001), despite similar dietary intakes of saturated and polyunsaturated fats, and cholesterol. Both the RTx patients and controls ingested a low amount of polyunsaturated fats [mean (SD) percent of total calories (E%) 4.8 (1.3) and 4.6 (1.5), respectively] and an excessive amount of saturated fats [mean (SD) E% 14.4 (2.4) and 14.1 (2.8), respectively]. In multiple regression analyses, dietary fibre was negatively associated with serum TC concentration. The standard deviation score for body mass index was negatively associated with serum concentration of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein diameter, and positively with serum triglyceride concentration. In addition, dietary total fat intake was positively associated with serum HDL-C. In conclusion, the higher prevalence of dyslipidaemia in our paediatric RTx patients than in the controls was not explained by the diet. However, the type of fat consumed implicates the counselling for a healthier dietary lifestyle, with an increase in the ingestion of polyunsaturated fats and a decrease in that of saturated fats.

Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density lipoprotein oxidation.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects. METHODS: Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO(3)(-)) determination and plasma oxidized LDL was determined by a capture ELISA. RESULTS: Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels. CONCLUSIONS: There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.

Lipoprotein docosapentaenoic acid is associated with serum matrix metalloproteinase-9 concentration.

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.