Complete Genome Sequences of Chop, DelRio, and GrandSlam, Three Phages Isolated from Soil in Central Arkansas.

Chop, DelRio, and GrandSlam are phage with a morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage.

Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance.

Background: The purpose of this study was to determine whether dietary manipulation can reliably induce early-stage atherosclerosis and clinically relevant changes in vascular function in an established, well-characterized non-human primate model.

Methods: We fed 112 baboons a high-cholesterol, high-fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy.

Plasma lipidomic profile signature of hypertension in Mexican American families: specific role of diacylglycerols.

Both as a component of metabolic syndrome and as an independent entity, hypertension poses a continued challenge with regard to its diagnosis, pathogenesis, and treatment. Previous studies have documented connections between hypertension and indicators of lipid metabolism. Novel technologies, such as plasma lipidomic profiling, promise a better understanding of disorders in which there is a derangement of the lipid metabolism.

A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation.

Background: Metabolic syndrome (MetS) is an aberration associated with increased risk for cancer and inflammation. Adiponectin, an adipocyte-produced abundant protein hormone, has countering effect on the diabetogenic and atherogenic components of MetS. Plasma levels of adiponectin are negatively correlated with onset of cancer and cancer patient mortality.

Identification of candidate genes encoding an LDL-C QTL in baboons.

Cardiovascular disease (CVD) is the leading cause of death in developed countries, and dyslipidemia is a major risk factor for CVD. We previously identified a cluster of quantitative trait loci (QTL) on baboon chromosome 11 for multiple, related quantitative traits for serum LDL-cholesterol (LDL-C). Here we report differentially regulated hepatic genes encoding an LDL-C QTL that influences LDL-C levels in baboons.

Variability in associations of phosphatidylcholine molecular species with metabolic syndrome in Mexican-American families.

Plasma lipidomic studies using high performance liquid chromatography and mass spectroscopy offer detailed insights into metabolic processes. Taking the example of the most abundant plasma lipid class (phosphatidylcholines) we used the rich phenotypic and lipidomic data from the ongoing San Antonio Family Heart Study of large extended Mexican-American families to assess the variability of association of the plasma phosphatidylcholine species with metabolic syndrome. Using robust statistical analytical methods, our study made two important observations.

Novel associations of nonstructural Loci with paraoxonase activity.

The high-density-lipoprotein-(HDL-) associated esterase paraoxonase 1 (PON1) is a likely contributor to the antioxidant and antiatherosclerotic capabilities of HDL. Two nonsynonymous mutations in the structural gene, PON1, have been associated with variation in activity levels, but substantial interindividual differences remain unexplained and are greatest for substrates other than the eponymous paraoxon. PON1 activity levels were measured for three substrates-organophosphate paraoxon, arylester phenyl acetate, and lactone dihydrocoumarin-in 767 Mexican American individuals from San Antonio, Texas.

Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease.

Preeclampsia (PE) is a serious complication of pregnancy, which is highly correlated with later life cardiovascular disease (CVD). Many risk factors are common for both diseases, but the contribution of shared genes remains to be determined. In this study, we used an integrative strategy to assess lipid traits as risk factors for PE and CVD by whole genome transcriptional profiling performed on Norwegian decidua basalis tissues (N = 95) from preeclamptic and normal pregnancies and on blood lymphocytes (N = 1240) from the San Antonio Family Heart Study (SAFHS).

Effects of diet on genetic regulation of lipoprotein metabolism in baboons.

Several measures of lipoprotein phenotype are significant predictors of cardiovascular risk. Although such lipoprotein phenotypes are under strong genetic control, it is not clear to what extent they are controlled by the same - and by different - genes and whether these relationships may be altered in different dietary environments. Therefore, we measured six lipoprotein traits (three LDL traits - LDLC and apoB concentrations and LDL size - and three HDL traits - HDLC and apoA1 concentrations and HDL size) on each of three diets differing in level of fat and cholesterol.

Localization of genes for V+LDL plasma cholesterol levels on two diets in the opossum Monodelphis domestica.

Plasma cholesterol levels among individuals vary considerably in response to diet. However, the genes that influence this response are largely unknown. Non-HDL (V+LDL) cholesterol levels vary dramatically among gray, short-tailed opossums fed an atherogenic diet, and we previously reported that two quantitative trait loci (QTLs) influenced V+LDL cholesterol on two diets.

Genetic regulation of endothelial inflammatory responses in baboons.

Objective: To investigate the genetic contributions to the expression of cell surface adhesion molecules on endothelial cells (ECs) and to the release by ECs of chemokines, which are responsible for local inflammation.

Methods And Results: Monocyte adhesion to ECs and transmigration across the endothelial barrier are the key steps in the formation of atherosclerotic plaques and the rupture of the existing plaques. Biopsy specimens were obtained from the femoral arteries of 131 pedigreed baboons (65 males and 66 females) aged 10.

Cholesteryl ester transfer protein polymorphism (TaqIB) associates with risk in postinfarction patients with high C-reactive protein and high-density lipoprotein cholesterol levels.

Objective: To investigate the roles of inflammation and a cholesteryl ester transfer protein (CETP) polymorphism potentially related to recent findings demonstrating coronary risk with increasing high-density lipoprotein cholesterol (HDL-C) level.

Methods And Results: A novel graphical exploratory data analysis tool allowed the examination of coronary risk in postinfarction patients relating to HDL-C and C-reactive protein levels. Results demonstrated a high-risk subgroup, defined by high HDL-C and C-reactive protein levels, exhibiting larger HDL particles and lower lipoprotein-associated phospholipaseA(2) levels than lower-risk patients.

Chemerin is associated with metabolic syndrome phenotypes in a Mexican-American population.

Context: Chemerin is a novel adipokine previously associated with metabolic syndrome phenotypes in a small sample of subjects from Mauritius.

Objective: The aim of the study was to determine whether plasma chemerin levels were associated with metabolic syndrome phenotypes in a larger sample from a second, unrelated human population.

Design, Setting, Patients, And Intervention: Plasma samples were obtained from the San Antonio Family Heart Study (SAFHS), a large family-based genetic epidemiological study including 1431 Mexican-American individuals.

Localization of multiple pleiotropic genes for lipoprotein metabolism in baboons.

We employed a novel approach to identify the key loci that harbor genes influencing lipoprotein metabolism in approximately 2,000 pedigreed baboons fed various diets differing in levels of fat and cholesterol. In this study, 126 overlapping traits related to both LDL and HDL metabolism were normalized and subjected to genome-wide linkage screening. As was expected, the traits were highly, but not completely, correlated.

Effects of rosuvastatin on electronegative LDL as characterized by capillary isotachophoresis: the ROSARY Study.

Electronegative LDL, a charge-modified LDL (cm-LDL) subfraction that is more negatively charged than normal LDL, has been shown to be inflammatory. We previously showed that pravastatin and simvastatin reduced the electronegative LDL subfraction, fast-migrating LDL (fLDL), as analyzed by capillary isotachophoresis (cITP). The present study examined the effects of rosuvastatin on the more electronegative LDL subfraction, very-fast-migrating LDL (vfLDL), and small, dense charge-modified LDL (sd-cm-LDL) subfractions.

Lp(a) and risk of recurrent cardiac events in obese postinfarction patients.

Studies of recurrent coronary events in obese postinfarction patients show mixed results despite potential importance of obesity-related pathophysiologic processes and associated markers in establishing and predicting risk. The study aim was to determine specific markers of recurrent risk in obese postinfarction patients. Nondiabetic patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study were classified according to BMI as normal weight (<25 kg/m(2)), overweight (25.

Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol concentration in baboons fed an atherogenic diet.

Both lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity, a biomarker of inflammation, and concentration of its primary associated lipoprotein, LDL, are correlated with adverse coronary outcomes. We previously reported a quantitative trait locus (QTL) corresponding to HSA2p24.3-p23.

Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans.

Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genetic correlations with other phenotypes related to risk of CVD in Mexican-Americans.

Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in nonhyperlipidemic postinfarction patients.

Objective: Nonhyperlipidemic postinfarction patients are at high risk for recurrent coronary events by virtue of incident myocardial infarction (MI); however, few studies assess risk beyond incident MI. The aim of this study was to assess such risk as a function of 37 atherosclerosis-associated genetic polymorphisms and 17 blood marker variables.

Methods And Results: Screening of polymorphisms in nonhyperlipidemic postinfarction patients revealed significant risk only for the 4G/5G insertion/deletion polymorphism in the promoter of the plasminogen-activator inhibitor-1 (PAI-1) gene.

The genes influencing adiponectin levels also influence risk factors for metabolic syndrome and type 2 diabetes.

Results from previous studies suggest that adiponectin levels are associated with risk factors for cardiovascular disease and type 2 diabetes mellitus; however, the genetic and/or environmental components of this relationship have not been characterized. The aims of this study were (1) to assess the presence of pleiotropy between adiponectin levels and risk factors for cardiovascular disease and (2) to study the association of circulating levels of adiponectin with risk factors for cardiovascular disease in the absence and presence of obesity in Mexican American adults from the San Antonio Family Heart Study. Body composition and circulating levels of adiponectin, leptin, and lipid subfractions and measurements of glucose metabolism were measured in 898 subjects.

Decreased bone mineral density is correlated with increased subclinical atherosclerosis in older, but not younger, Mexican American women and men: the San Antonio Family Osteoporosis Study.

An association has been reported between cardiovascular disease (CVD) and osteoporosis, perhaps attributable to the presence of common risk factors. To assess this possibility, we measured areal bone mineral density (BMD) and carotid artery intimal medial thickness (IMT), a measure of preclinical atherosclerosis, in 535 women and 335 men from the San Antonio Family Osteoporosis Study. Variance decomposition methods were used to determine whether cross-sectional measures of areal BMD (measured by dual-energy X-ray absorptiometry) of the total hip, spine, and forearm were correlated with IMT, serum lipids, and/or C-reactive protein (CRP), a marker of inflammation, after accounting for known environmental factors.

Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes.

Quantitative differences in gene expression are thought to contribute to phenotypic differences between individuals. We generated genome-wide transcriptional profiles of lymphocyte samples from 1,240 participants in the San Antonio Family Heart Study. The expression levels of 85% of the 19,648 detected autosomal transcripts were significantly heritable.

Vitamin E dietary supplementation significantly affects multiple risk factors for cardiovascular disease in baboons.

Background: Oxidative stress is a widely accepted risk factor for cardiovascular disease (CVD), but the CVD benefit of dietary antioxidants, such as vitamin E, is controversial.

Objective: Therefore, we have investigated, in the baboon model, the effects of dietary vitamin E supplementation on risk factors for CVD.

Design: Pedigreed baboons (n = 251) were fed 2 atherogenic diets, high in fat and cholesterol, that differed in vitamin E concentrations.

Identification of promoter variants in baboon endothelial lipase that regulate high-density lipoprotein cholesterol levels.

Background: High-density lipoprotein cholesterol (HDL) levels are a major risk factor for cardiovascular disease. Previously we identified a quantitative trait locus on baboon chromosome 18 that regulates HDL. From positional cloning studies and expression studies, we identified the endothelial lipase gene (LIPG) as the primary candidate gene for the quantitative trait locus.

Effects of reconstituted HDL on charge-based LDL subfractions as characterized by capillary isotachophoresis.

Modified LDL in human plasma including small, dense LDL (sdLDL) and oxidized LDL carries a more negative charge than unmodified LDL and is atherogenic. We examined the effects of apolipoprotein A-I (apoA-I)/POPC discs on charge-based LDL subfractions as determined by capillary isotachophoresis (cITP). Three normal healthy subjects and seven patients with metabolic disorders were included in the study.