Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models

Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models

Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (

Autoantibody Profiling for Lung Cancer Screening Longitudinal Retrospective Analysis of CT Screening Cohorts

Recommendations for lung cancer screening present a tangible opportunity to integrate predictive blood-based assays with radiographic imaging. This study compares performance of autoantibody markers from prior discovery in sample cohorts from two CT screening trials. One-hundred eighty non-cancer and 6 prevalence and 44 incidence cancer cases detected in the Mayo Lung Screening Trial were tested using a panel of six autoantibody markers to define a normal range and assign cutoff values for class prediction. A cutoff for minimal specificity and best achievable sensitivity were applied to 256 samples drawn annually for three years from 95 participants in the Kentucky Lung Screening Trial. Data revealed a discrepancy in quantile distribution between the two apparently comparable sample sets, which skewed the assay’s dynamic range towards specificity. This cutoff offered 43% specificity (102/237) in the control group and accurately classified 11/19 lung cancer samples (58%), which included 4/5 cancers at time of radiographic detection (80%), and 50% of occult cancers up to five years prior to diagnosis. An apparent ceiling in assay sensitivity is likely to limit the utility of this assay in a conventional screening paradigm. Pre-analytical bias introduced by sample age, handling or storage remains a practical concern during development, validation and implementation of autoantibody assays. This report does not draw conclusions about other logical applications for autoantibody profiling in lung cancer diagnosis and management, nor its potential when combined with other biomarkers that might improve overall predictive accuracy