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Objective/Background Expression patterns and association with cell specific gene expression signatures of the epigenetic regulator histone deacetylase 9 (HDAC9) and matrix metalloproteinase 12 (MMP12) in human plaque are not known. Methods This was a prospective cohort study. Genome wide expression analysis was performed in carotid, femoral, aortic plaques ( n = 68) and left internal thoracic (LITA) controls ( n = 28) and plaque histological severity assessed. Correlation and hierarchical cluster analysis was utilised. Results HDAC9 was associated with MMP12 expression in carotid plaques ( r = .46, p = .012) and controls ( r = −.44, p = .034). HDAC9 and MMP12 clustered with inflammatory macrophage markers but not with smooth muscle cell (SMC) rich markers. In plaques from all arterial sites, MMP12 but not HDAC9 showed positive correlation ( p < .05) with M2 and M4 polarized macrophage markers, and negative correlation with SMC rich signatures. In the carotid plaques, all M4 macrophage markers associated with MMP12 and HDAC9. The negative association of MMP12 with SMC rich signatures was pronounced in the carotid plaques. Neither HDAC9 nor MMP12 associated consistently with plaque stabilisation or thrombosis related genes. Immunohistochemistry further supported the association between HDAC9 and MMP12 in atherosclerotic plaques. Conclusion M4 macrophages are a possible source for HDAC9 and MMP12 expression in advanced human plaques. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The role of neuropeptide Y (NPY) and its gene polymorphisms in the development of atherosclerosis has become increasingly evident. In asthma, NPY has been shown to be involved as immunomodulator. In this study, we investigated the role of two functional NPY polymorphisms, NPY-Leu7Pro (rs16139) and NPY-399C/T (rs16147) and obesity for the development of asthma as well as atherosclerosis in asthmatic and non-asthmatic subjects. Also, we measured heart rate variability (HRV) and NPY in serum since these might contribute through these polymorphisms to both diseases. Methods and results: Thousand hundred and seventy six Finnish young adults were genotyped and three groups (G1–G3) were formed based on the observed diplotypes. The NPY-Pro7 allele always co-existed with the NPY-399T allele indicating complete linkage disequilibrium. Here we show that overweight (BMI⩾25kg/m2) was associated with 2.5-fold increased risk for asthma in subjects with the NPY-399T allele without NPY-Pro7 allele (G2, n =716). Overweight was also associated with increased atherosclerosis determined by carotid intima media thickness (cIMT), but asthma seemed to be more significant determinant than overweight in determing cIMT having a decreasing effect. NPY concentration in serum was diplotype-driven (G1=792.2(29.5), G2=849.0(18.9), G3=873.9(45.2) pg/ml) and correlated positively with cIMT in the group having NPY-Pro7 allele (G3, n =142). However, the subjects with asthma had a negative NPY-cIMT relationship. Total HRV was increased in asthma and correlated negatively with cIMT irrespective of the NPY genotype. Conclusions: Overweight together with the NPY-399T allele without NPY-Pro7 allele was associated with increased risk for asthma. Atherosclerosis was decreased in subjects with asthma depending on the NPY genotype. The results reveal novel insights into the genetics and biology of the relationship of atherosclerosis and asthma. [Copyright &y& Elsevier]

Abstract: The effects of canola-type rapeseed oil (RSO) on serum lipids, plasma fibrinogen, lipid oxidation and fatty acids were studied in three groups of subjects, two of which had not been consuming fish in their habitual diets. Forty-two volunteers (35 women, 7 men, 16–62 years) replaced fat with RSO for 6 weeks in a parallel design. The average cholesterol and fibrinogen concentrations were 5.0mmol/l and 2.6g/l, respectively. The intake of α-linolenic acid (α-LLA) was doubled. Efficient competitive inhibition by α-LLA was seen as a decrease in long-chain (LC) n-6 PUFA at 3 weeks. Elevated fibrinogen (2.6–3.9g/l) decreased by 0.95g/l at 6 weeks. Docosahexaenoic acid (22:6n-3) in plasma phospholipids increased at low fibrinogen levels only. The associations and changes in plasma C18 and LC PUFA followed the competitive and metabolic principles of the body, and especially in the case of n-3 PUFA according to the recycling pathway. [Copyright &y& Elsevier]

The purpose of the study was to analyse the generalisability and geographic transportability of survival estimates produced by commonly used prognostic factors. We compared the influence of tumour size, histologic grade, axillary nodal status, oestrogen and progesterone receptor contents, age at diagnosis and two prognostication schemes (the Nottingham Prognostic Index and St. Gallen criteria) in two nationwide cohorts of patients diagnosed with breast cancer in 1991-2, the FinProg (n=2923, Finland) and the SEER series (n=43,249, the United States (US)). Eight-year estimates of breast cancer-specific (84% versus 80%), relative (86% versus 83%), and overall (70% versus 69%) survival were slightly more favourable in the SEER than in the FinProg series, respectively. Despite differences in demographic variables and the frequency of use of adjuvant therapies and mammography screening between the series, the prognostic factors examined produced close to overlapping survival curves with similar shapes. The results suggest that quantitative survival estimates based on frequently used prognostic factors and prognostication schemes are generalisable and transportable between large, unselected cohorts of breast cancer patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the associations of temperament traits and temperament profiles (i.e., the combinations of multiple traits) with adulthood educational attainment. The participants were 837 women and 592 men from a population-based cohort study. Temperament was assessed with the Temperament and Character Inventory (TCI) based on the Psychobiological Model of Temperament and Character. Analyses were conducted with linear regression analyses and with analysis of variance (ANOVA). In both genders, high harm avoidance was associated with lower educational attainment. High persistence among women and high reward dependence among men were related to higher educational attainment. Novelty seeking was not associated with educational attainment in either gender. Among men explosive and methodical temperament profiles were associated with lower educational attainment while reliable and passionate temperament profiles were associated with higher educational attainment. Temperament may play an important role in lifelong learning and academic performance over different developmental transitions. [ABSTRACT FROM AUTHOR]

Abstract: In a previous study, we observed a higher incidence of dyslipidemia in pediatric renal recipients compared with liver recipients. In the present study, we measured common carotid artery intima-media thickness (IMT) in 13 pediatric renal recipients, 9 liver recipients, and 26 control individuals with median age of 11.4, 10.8, and 12.0 years, respectively. The patients were studied from 0.2 to 10.8 years after renal transplantation (RTx) or liver transplantation (LTx). An experienced radiologist (T.K.) blinded to the status of the children measured the IMT using a high-resolution B-mode ultrasonography method. In patients who underwent RTx or LTx, serum fasting lipid profile, estimates of renal and liver function, and glucose metabolism were determined. Children undergoing RTx or LTx more often had hypertension compared with the control individuals (P = .004). Before transplantation, dyslipidemia was greater in patients undergoing RTx compared with those undergoing LTx (P < .05). Children who underwent RTx, compared with those who underwent LTx or control individuals, had thicker mean IMT at the 6 sites measured (mean [SD], 0.57 [0.07], 0.51 [0.05], and 0.53 [0.06] mm, respectively; P = .02]. As a result of linear regression in renal recipients, variability of glomerular filtration rate (<60 mL/min/1.73 m2 vs normal) accounted for 43.3% of variability of the mean of maximal IMT (B = 8.9; SE = 3.1; P = .01). Variability of pre-RTx serum triglyceride concentration (B = 1.6; SE = 0.6; P = .03) and actual triglyceride concentration (B = 10.3; SE = 2.2; P = .002) accounted for 82.2% of variability of maximal IMT. Our findings support previous data on the importance of maintenance of good graft function with sufficient but not overly efficient immunosuppression after transplantation in prevention of future cardiovascular disease. [Copyright &y& Elsevier]

Abstract: Objective: Serum C-reactive protein (CRP) is an independent risk factor for cardiovascular disease and metabolic syndrome (MetS). The aim of this study was to analyze the CRP gene allelic variations in the Turkish adult risk factor (TARF) study and relate them with serum CRP levels as well as MetS and its components. Methods: We analyzed CRP gene polymorphisms (−286C>T>A [rs3091244], +1444C>T [rs1130864], +1059G>C [rs1800947], and +1846G>A [rs1205]) as well as their haplotypes, in addition to measuring CRP levels (n =1138) and collecting risk factor data from 1987 adults (mean age 54.3±11.9 years, 51.3% women) participating in the TARF Study. MetS was defined by using the criteria of the National Cholesterol Education Program modified for pre-diabetes and in men for abdominal obesity. Results: After adjustment for the major cardiovascular risk factors, four CRP SNPs (−286C>T>A, +1059G>C, +1444C>T, and +1846G>A) were significantly associated with serum CRP levels in women (p <0.05), whereas the −286C>T>A and +1444C>T polymorphisms were associated with CRP levels in men (p <0.05). The haplotype analyses revealed four common CRP haplotypes. The haplotype 1 (CGCA) in women and the haplotype 3 (TGTG) in men were associated with serum CRP levels and hypertension (p <0.05). However, no haplotype association was observed for MetS or its components. Conclusion: CRP gene allelic variation is associated with serum CRP levels as well as hypertension in Turkish adults. [Copyright &y& Elsevier]

Abstract: Although C-reactive protein (CRP) is known to predict cardiovascular events, its status as a causal risk factor is still controversial. CRP gene single nucleotide polymorphisms (SNPs) have been shown to associate with CRP concentration, but no direct independent effect on early atherosclerotic changes has been demonstrated. We aimed to determine if CRP gene polymorphisms or haplotypes are associated with CRP concentration or carotid artery compliance (CAC), an indicator of subclinical atherosclerosis. We genotyped CRP gene polymorphisms −717A>G, −286C>T>A, +1059G>C, +1444C>T and +1846G>A and measured CRP concentration and CAC in 2283 young adults participating in The Cardiovascular Risk in Young Finns Study. A strong association was found between CRP genotypes and CRP concentration, which was also seen at the haplotype level. Linear regression analysis showed an independent effect of each SNP on CRP concentration after adjustment for risk factors, except for +1444 in males. Moreover, −286C>T>A, +1444C>T and +1846G>A were associated with CAC in males, but not in females. Men carrying the SNP −286 allele C had increased CAC after adjusting for risk factors. These data suggest that the presence of high producer CRP genotype is deleterious to carotid elasticity in men. [Copyright &y& Elsevier]

Pravastatin decreases serum MMP-9 concentration in clinically healthy men. This may reflect reduction of nonsymptomatic chronic arterial inflammation. [ABSTRACT FROM AUTHOR]