scholarly journals CD73 Promotes Age-Dependent Accretion of Atherosclerosis

2020 ◽  
Vol 40 (1) ◽  
pp. 61-71 ◽  
Author(s):  
Nadia R. Sutton ◽  
Diane Bouïs ◽  
Kris M. Mann ◽  
Imran M. Rashid ◽  
Alexandra L. McCubbrey ◽  
...  
Keyword(s):  
Plasma Lipid ◽  
Early Time ◽  
Adenosine Monophosphate ◽  
Lipid Levels ◽  
Surface Versus ◽  
Lipid Catabolism ◽  
Significant Reversal ◽  
Age Dependent ◽  
The Impact

Objective: CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis. Approach and results: Mice doubly deficient in CD73 and ApoE (apolipoprotein E; ( cd73 − /− /apoE −/− ) were generated, and the extent of aortic atherosclerotic plaque was compared with apoE −/− controls at 12, 20, 32, and 52 weeks. By 12 weeks of age, cd73 −/− /apoE −/− mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in apoE −/− controls, P <0.005). By 20 weeks of age, this difference disappeared (2.9±0.4% versus 3.3±0.7%). A significant reversal in phenotype emerged at 32 weeks (9.8±1.2% versus 18.3±1.4%; P <0.0001) and persisted at the 52 week timepoint (22.4±2.1% versus 37.0±2.1%; P <0.0001). The inflammatory response to aging was found to be comparable between cd73 −/− /apoE −/− mice and apoE −/− controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels ( cd73 −/− /apoE −/− versus apoE −/− at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well], P <0.001). Conclusions: At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.

W15-IS-002 Role of farnesoid X receptor (FXR) in control of plasma lipid levels

2005 ◽  
Vol 6 (1) ◽  
pp. 95-96
Author(s):  
T. Claudel ◽  
B.M. Elzinga ◽  
V. Bloks ◽  
B. Staels ◽  
P.J. Voshol ◽  
...  
Keyword(s):  
Plasma Lipid ◽  
Farnesoid X Receptor ◽  
Lipid Levels

scholarly journals Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

2020 ◽  
Vol 13 (4) ◽  
Author(s):  
Zhe Wang ◽  
Han Chen ◽  
Traci M. Bartz ◽  
Lawrence F. Bielak ◽  
Daniel I. Chasman ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Plasma Lipid ◽  
Low Frequency ◽  
Environment Interaction ◽  
Lipid Levels ◽  
Protein Coding ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Coding Variants

Background: Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. Methods: In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered. Results: We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci ( PCSK9 , LPA , LPL , LIPG , ANGPTL4 , APOB , APOC3 , and CD300LG ) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered ( P =6.65×10 −6 for the interaction test) and replicated at nominal significance level ( P =0.013) in SMC5 . Conclusions: In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.

scholarly journals Role of Rare and Low Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

2019 ◽  
Author(s):  
Zhe Wang ◽  
Han Chen ◽  
Traci M. Bartz ◽  
Lawrence F. Bielak ◽  
Daniel I. Chasman ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Association Studies ◽  
Plasma Lipid ◽  
Low Frequency ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
Lipid Levels ◽  
Gxe Interaction ◽  
Fasting Plasma

AbstractBackgroundAlcohol intake influences plasma lipid levels and such effects may be modulated by genetic variants.ObjectiveWe aimed to characterize the role of aggregated rare and low-frequency variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.DesignIn the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, fasting plasma triglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-c and LDL-c) were measured in 34,153 European Americans from five discovery studies and 32,275 individuals from six replication studies. Rare and low-frequency protein coding variants (minor allele frequency ≤ 5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction (GxE) test and a joint test of genetic main and GxE interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least two drinks per week, were considered.ResultsWe discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3 and CD300LG) remained significant after conditioning on the common index single nucleotide polymorphism (SNP) identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on TG was discovered at a Bonferroni corrected significance level (p-value <5×10−5) and replicated (p-value <0.013 for the interaction test) inSMC5.ConclusionsIn conclusion, this study applied new gene-based statistical approaches to uncover the role of rare and low-frequency variants in gene-alcohol consumption interactions on lipid levels.

The Role of Plasma Lipid Levels as Markers of Recovery of Liver Function after Hepatectomy

2014 ◽  
Vol 4 (36) ◽  
pp. 5756-5769
Author(s):  
Sophocles Lanitis ◽  
Evangelos Lolis ◽  
George Sgourakis ◽  
Panagiotopoulou Katerina ◽  
Kalypso Barbati ◽  
...  
Keyword(s):  
Liver Function ◽  
Plasma Lipid ◽  
Lipid Levels

Abstract MP62: Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Zhe Wang ◽  
Han Chen ◽  
Daniel I Chasman ◽  
Ching-Ti Liu ◽  
Raymond Noordam ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Plasma Lipid ◽  
Low Frequency ◽  
Joint Analysis ◽  
Genome Wide Association Studies ◽  
Lipid Levels ◽  
Gxe Interaction ◽  
Functional Variants ◽  
Fasting Plasma

Introduction: Alcohol intake modifies plasma lipid levels and such effects may be modulated by genetic variants. We use emerging statistical methods that extend well-established common variant approaches to characterize the role of aggregated rare and low-frequency variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. Methods: Up to 247,870 exonic variants on the Illumina HumanExome BeadChip and fasting plasma triglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-c and LDL-c) were measured in 46,443 European Americans from 4 studies (the Atherosclerosis Risk in Communities (ARIC) study, the Framingham Heart Study, the Netherlands Epidemiology of Obesity Study and the Women’s Genome Health Study) of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Using the gene-based rareGE method, we conducted exome-wide gene-environment (GxE) tests with genetic main effects estimated as fixed and random effects, and a joint analysis of genetic main and GxE interaction effects. Rare and low-frequency (minor allele frequency ≤ 5%) functional variants, (i.e. frameshift, nonsynonymous, stop/gain, stop/loss, and splicing) were aggregated by genes. Two dichotomous self-reported alcohol consumption variables, current drinker (at least 1 drink per week, yes/no) and regular drinker (at least 2 drinks per week, yes/no) were considered. A sample size weighted Z-test (weighted Stouffer’s method) was used to meta-analyze study-specific p -values. Exome-wide significance level was set at p < 3.7*10 -6 (0.05/13368 genes), using a Bonferroni procedure to correct for multiple testing. Results: We identified 24 gene-lipid associations at 13 known lipid loci (within 500kb) harboring rare and low-frequency variants through the joint analysis. In ARIC, numerous genes ( PCSK9, LPL, LIPG, ANGPTL4, APOB, APOC3-A5 ) remained significant after conditioning on common index single nucleotide polymorphisms (SNPs), suggesting an independent role for rare variants at loci highlighted by previous genome-wide association studies. However, no significant gene-alcohol interactions were observed with rare and low-frequency variants on TG, HDL-c or LDL-c. Conclusion: This study applied new statistical approaches to investigate the role of rare and low-frequency variants in gene-alcohol consumption interactions on lipid levels. Results show promise for other larger scale studies analyzing rare variant GxE interactions.

Regulation of plasma lipid levels by plasma viscosity in nephrotic rats

1985 ◽  
Vol 248 (1) ◽  
pp. E10-E14 ◽  
Author(s):  
S. Yedgar ◽  
O. Eilam ◽  
E. Shafrir
Keyword(s):  
Lipid Level ◽  
Plasma Lipid ◽  
Plasma Viscosity ◽  
Cultured Hepatocytes ◽  
Lipid Levels ◽  
Very Low Density Lipoproteins ◽  
Extracellular Medium ◽  
Cholesterol Levels

The viscosity of the extracellular medium of cultured hepatocytes has been shown to be a regulator of the secretion and synthesis of very low-density lipoproteins (Yedgar et al., J. Biol. Chem. 257: 2188-2192, 1982). At present, the role of plasma viscosity in regulation of plasma lipoprotein levels was examined in vivo using nephrotic hyperlipidemic rats. Plasma viscosity was increased by injection of macromolecules: simultaneously with induction of nephrosis by aminonucleoside; and after the lipid level had reached its maximum. In experiment 1 the elevation of plasma viscosity (which persisted for at least 2 days) delayed the development of the hyperlipidemia by at least 2 days. In experiment 2 increasing the plasma viscosity reduced plasma triglyceride and cholesterol levels by 70 and 40%, respectively, within 2 days. The hyperlipidemia was accompanied by increased plasma viscosity. The contribution of lipoproteins to plasma viscosity was 27% in the nephrotic-hyperlipidemic rats, compared with 4% in normal rats. It is suggested that plasma viscosity regulates lipoprotein levels in vivo concordant with the observation in cultured hepatocytes.

The role of cardiorespiratory fitness on plasma lipid levels

2015 ◽  
Vol 13 (11) ◽  
pp. 1177-1183 ◽  
Author(s):  
Parham Parto ◽  
Carl J Lavie ◽  
Damon Swift ◽  
Xuemei Sui
Keyword(s):  
Cardiorespiratory Fitness ◽  
Plasma Lipid ◽  
Lipid Levels

scholarly journals Detection of the Low Density Lipoprotein Receptor Gene Pvuii Intron 15 Polymorphism Using the Polymerase Chain Reaction: Association With Plasma Lipid Traits in Healthy Men and Women

1998 ◽  
Vol 13 (4) ◽  
pp. 209-220 ◽  
Author(s):  
V. Gudnason ◽  
T. Zhou ◽  
K. Thormar ◽  
S. Baehring ◽  
J. Cooper ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Splice Acceptor Site ◽  
Low Density ◽  
Lipid Levels ◽  
Men And Women ◽  
The Impact

We have used anchored PCR to amplify and sequence 1400bp of the 15th intron of the Low Density Lipoprotein (LDL) receptor gene, and have determined oligonucleotides and conditions for the genotyping of the previously reported Pvull polymorphism. The cutting site (CAGCTG) is created by the transition of a CpG to a TpG within the sequence CAGCCG at a position roughly 600bp 5' from the splice acceptor site of exon 16. Genotype was determined in three populationbased samples of healthy individuals. In a group of 318 men and women from Iceland the frequencies of the Intron-15 T (cutting) allele was 0.23 (95% CI, 0.19-0.28) and was similar in men and women. In two groups of men from England (n=385) and Scotland (n=320), the frequency was similar, being 0.23 (0.19-0.27) and 0.25 (0.22-0.28) respectively. Individuals who were homozygous for the T allele had lower levels oftotal-cholesterol triglycerides and apolipoprotein B, than those with other genotypes, and in the combined group of UK men this effect reached statistical significance; compared to the CIC group, the TIT group had 6% lower cholesterol (p=0.02) and 15% lower triglycerides (p=0.03). The lowering effect associated with the TIT genotype was greater in men who were in the lowest terti Ie of body mass index (<25kg/m2) and for the trait of apoB levels, this genotype x obesity interaction was statistically significant (p=0.01). We thus confirm the association between this allele and lower levels of plasma lipid levels previously reported. The availability of a PCR-based method to detect this polymorphism will facilitate further investigation of the impact of LDL-receptor gene variation in determining lipid levels.

The impact ofd-Trp6 LH-RH on plasma lipid levels

1996 ◽  
Vol 13 (3) ◽  
pp. 223-227 ◽  
Author(s):  
Gil A. Goldman ◽  
Alex Schoenfeld ◽  
Jardena Ovadia ◽  
Benjamin Fisch
Keyword(s):  
Plasma Lipid ◽  
Lipid Levels ◽  
Lh Rh ◽  
The Impact
Sign in / Sign up

Export Citation Format

Share Document