Higher Apo Research Articles

KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE \u03b54-positive cognitively normal adults with high A\u03b2-amyloid burden

A single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein (KIBRA) gene has been associated with cognition and hippocampal volume in cognitively normal (CN) individuals. However, the impact of rs17070145 on longitudinal cognitive decline and hippocampal atrophy in CN adults at greatest risk of developing Alzheimer’s disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippocampal atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype. We reveal that whilst limited independent effects of KIBRA genotype were observed, there was an interaction with APOE in CN adults who presented with high Aβ-amyloid levels across study duration. In comparison to APOE ε4-ve individuals carrying the rs17070145-T allele, significantly faster rates of cognitive decline (global, p = 0.006; verbal episodic memory, p = 0.004), and hippocampal atrophy (p = 0.04) were observed in individuals who were APOE ε4 + ve and did not carry the rs17070145-T allele. The observation of APOE effects in only non-carriers of the rs17070145-T allele, in the presence of high Aβ-amyloid suggest that carriers of the rs17070145-T allele are conferred a level of resilience to the detrimental effects of high Aβ-amyloid and APOE ε4.

Associations of lipoproteins with cardiovascular and infection-related outcomes in patients receiving hemodialysis

In hemodialysis (HD) patients, higher lipid levels are associated with lower mortality. Lipid-lowering therapy does not reduce all-cause mortality or cardiovascular (CV) mortality. Lipoproteins play a role in the innate immune system. Our objective was to determine whether protection from infection might counterbalance adverse CV outcomes associated with lipoproteins. We examined associations between serum apolipoprotein (Apo) A1, B, C2, C3, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol and triglyceride levels and infectious mortality or hospitalization, CV mortality or hospitalization, and all-cause mortality in 433 prevalent HD patients. Cox models with time-varying apolipoprotein concentrations collected every 6months for up to 2years were used for analyses. Median follow-up time for all-cause mortality was 2.7years (25th-75th percentile range: 2.2-3.4years). One hundred seventy-nine (41%) patients had an infection-related event. In multivariable models, higher Apo B and LDL were associated with lower risks of infection-related outcomes (hazard ratio Apo B 0.92 [95% confidence interval 0.86-0.99 per 10mg/dL, P=.03]; hazard ratio LDL 0.93 [95% confidence interval 0.87-1.00 per 10mg/dL, P=.05]). Sixty-three (15%) participants had a CV-related event. No significant associations were observed between lipoproteins and CV outcomes. Eighty-seven (20%) participants died. Higher Apo A1, Apo B, and Apo C3 were associated with lower risks of all-cause mortality. There was no interaction between the use of lipid-lowering medication and any of the outcomes. Associations of lipoproteins with lower risk of serious infection accompanied by no significant association with CV events may help to explain the paradoxical association between lipids and survival and lack of benefit of lipid-lowering therapies in HD.

Effect of long-term dietary sphingomyelin supplementation on atherosclerosis in mice.

Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels. SM consumption did not increase circulating SM levels or atherosclerosis in high fat-fed apoE-/- mice. Serum TMAO levels in C57BL/6 mice were low and had no effect atherosclerosis lesion development. Dietary SM supplementation significantly reduced atherosclerotic lesion area in the aortic arch of chow-fed apoE-/- mice. This study establishes that dietary SM does not affect circulating SM levels or increase atherosclerosis in high fat-fed apoE-/- mice, but it is anti-atherogenic in chow-fed apoE-/- mice.

Blood lipids and lipoproteins in relation to incidence and mortality risks for CVD and cancer in the prospective EPIC\u2013Heidelberg cohort

BackgroundCirculating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD.MethodsWe selected a case-cohort sample out of the prospective EPIC–Heidelberg study, including a random subcohort (n = 2739), and cases of cancer (n = 1632), cancer mortality (n = 761), CVD (n = 1070), and CVD mortality (n = 381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models.ResultsHigh levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HRapoB 0.71, 95% CI 0.52–0.98; HRTG 0.65, 0.46–0.92; and HRHDL 1.39, 1.01–1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HRLp(a) 1.43, 1.02–2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HRapo(a) 0.52, 0.30–0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HRTC 0.71, 0.54–0.94; HRHDL 0.67, 0.50–0.91; HRapo(a) 0.71, 0.54–0.93; and HRLp(a) 0.74, 0.57–0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments.ConclusionsThis prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.

Serum apolipoprotein B is inversely associated with eccentric left ventricular hypertrophy in peritoneal dialysis patients

The study aimed to examine the relationship of serum apolipoprotein B level with left ventricular (LV) structural and functional characteristics, in particular, LV remodeling parameters in peritoneal dialysis (PD) patients. A total of 182 patients with end-stage renal disease (ESRD) receiving PD were identified. Conventional echocardiography was performed for each patient, and echocardiographic characteristics were analyzed according to apo B quartile groups. Multivariate linear regression models were used to determine the associations between serum apo B and LV remodeling indices. A high serum apo B level was significantly related to the reduction in left atrium dimension (r=-0.20, P=0.011), LV dimensions (end-diastolic: r=-0.27, P=0.001; end-systolic: r=-0.24, P=0.003), peak velocities of early filling divided by peak velocities of atrial filling (r=-0.38, P<0.001), and LV volumetric dimension (end-diastolic: r=-0.27, P<0.001; end-systolic: r=-0.28, P<0.001). After adjustment for clinical confounding factors, the effect of serum apo B on LV eccentric remodeling modestly weakened but remained statistically significant (P=0.038), while other associations were not significant. In multivariate linear regression analysis, conventional lipid profiles were not significantly associated with LV eccentric remodeling, whereas serum apo B was an independent determinant of LV dilatation (β: -42.10, 95% CI -74.82 to -9.38, P=0.012). Serum apo B was significantly and inversely associated with LV dilatation, independently of conventional lipids and other CV risk factors in our ESRD patients undergoing PD. It suggested that low serum apo B level could be a powerful risk marker for eccentric left ventricular geometry remodeling and could be potentially used to risk-stratify PD patients.

Association between Apo B Levels in Mothers and in their Pre-school Age Offspring.

The study aims to determine the association between apo B levels in mothers and their pre-school offspring. Anthropometric measurement (e.g. BMI), lipids, lipoproteins, and apolipoproteins (e.g. apo B) levels in mothers and their children were obtained in November 2015 in Buenos Aires. Eighty-four children (42M) aged 5.3±1.6 years and their mothers aged 33.8±7.2 years were examined. The prevalence of overweight was 39.2 % (33) in mothers and 22.6 % (19) in children, and the prevalence of obesity was 38.1% (32) in mothers and 10.7% (9) in children. Multiple linear regression analysis showed that maternal apo B levels were associated with apo B levels in their offspring, adjusted for confounding variables (Beta=0.29; p=0.03; R2=0.25). Furthermore, offspring born to mothers with high apo B levels were six times likelier to have high apo B levels (OR), 5.7; (95% CI 1.3-25.5). This study suggests that maternal apo B levels were significantly associated with apo B concentration in their pre-school age children.

Apolipoprotein status in type 2 diabetes mellitus and its complications (Review).

Dyslipidaemia in type 2 diabetes mellitus (T2DM) is characterized by high plasma triglyceride concentrations, reduced high‑density lipoprotein concentrations and increased small density low‑density lipoprotein concentrations. Dyslipidaemia may lead to cardiovascular disease (CVD) and other complications. Apolipoproteins mainly comprise six species, apolipoprotein (apo)A, apoB, apoC, apoD, apoE and apoM, which are important components of plasma lipoproteins that carry lipids and stabilize the structure of lipoproteins. Complex metabolic disorders of apolipoproteins are present in T2DM, such as high plasma apoB, apoC‑II, apoC‑III and apoE concentrations, and low plasma apoA‑I and apoM concentrations, which are associated with dyslipidaemia and interrelated complications. Plasma concentrations of some apolipoproteins are also altered in T2DM with CVD or other complications. Several apolipoprotein polymorphisms are associated with diabetes susceptibility and/or lipid metabolism. The present review described the metabolic disorders of apolipoproteins in T2DM and its complications, and the relationship between each major apolipoprotein and T2DM, as well as the effects of apolipoprotein polymorphisms on diabetic susceptibility.

Chronic apical periodontitis as risk factor atherosclerosis and artery disease

Periodontitis is caused by bacteria that are present in periodontal tissues also under physiological condition. Neglected hygiene may increase the number of microorganisms and the formation of chronic apical periodontitis (CAP). The aim of the study was to evaluate changes in inflammatory expression (hsCRP and LpPLA2 in adult patients one year after the end of endodontic treatment, thereby the risk analysis of cardiovascular disease. Material and methods: Twenty-six patients who had history of inflammation outside the oral cavity were diagnosed with CAP before the treatment and one year after the end of endodontic treatment. The studied men and women were divided into two age groups: 50 above years (N = 13) and below 50 years (N = 13). In addition, the study groups were separated in relation to apoAI concentration, taking a cut-off of 150mg/dl. The therapeutic effect was achieved in 26 patients after endodontic treatment. The concentration of bio- chemical parameters – hsCRP and LpPLA2 as well as apoAI was evaluated using the commercially available methods. Statistical analysis was performed using the pair test for dependent samples. Results: In patients below 50 years of age and 1 year after the end of treatment a significant reduction in hsCRP and LpPLA2 level was observed. Similarly, a statistically significant decrese in LpPLA2 concentration was observed in patients with apoAI&gt;150 mg/dl. Conclusions: In patients &lt; 50years of age, after 1 year CAP treatment, the CAP inflammatory foci CAP were reduced and the inflammatory markers were normalized. Also in patients with a high apoAI level, reduced and the after treat suggested that elevated level of apoAI and LpPLA2 in HDL particles might reduce the inflammatory lesion size in CAP and might systemic complications. CAP, particularly in patients over 50 years of age and at an apoAI&lt;150mg/dl and higher level of LpPLA2, is a risk factor for atherosclerosis and destabiliza- tion of atherosclerotic plaque. Endodontic treatment should be induced in medication of atherosclerosis and its complications both in primary and secondary prevention.

Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity

Background:Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with metabolic disturbances including obesity, insulin resistance and diabetes mellitus. Here we investigate whether changes in the metabolic profile of PCOS women are driven by increased tendency to obesity or are specific features of PCOS related to increased testosterone levels.Design and methods:We conducted an NMR metabolomics association study of PCOS cases (n=145) and controls (n=687) nested in a population-based birth cohort (n=3127). Subjects were 31 years old at examination. The main analyses were adjusted for waist circumference (WC) as a proxy measure of central obesity. Subsequently, metabolite concentrations were compared between cases and controls within pre-defined WC strata. In each stratum, additional metabolomics association analyses with testosterone levels were conducted separately among cases and controls.Results:Overall, women with PCOS showed more adverse metabolite profiles than the controls. Four lipid fractions in different subclasses of very low density lipoprotein (VLDL) were associated with PCOS, after adjusting for WC and correction for multiple testing (P<0.002). In stratified analysis the PCOS women within large WC strata (⩾98 cm) had significantly lower high density lipoprotein (HDL) levels, Apo A1 and albumin values compared with the controls. Testosterone levels were significantly associated with VLDL and serum lipids in PCOS cases with large WC but not in the controls. The higher testosterone levels, adjusted for WC, associated adversely with insulin levels and HOMA IR in cases but not in the controls.Conclusions:Our findings show that both abdominal obesity and hyperandrogenism contribute to the dyslipidaemia and other metabolic traits of PCOS which all may negatively contribute to the long-term health of women with PCOS.

Assessment of serum apolipoprotein B and apolipoprotein A-1 and their ratio in healthy full term small for gestational age newborns.

Programmed changes in growth restricted fetuses can increase the risk of adulthood diseases due to elevated serum cholesterol and apolipoprotein-B (Apo-B) concentrations. Increasing evidence demonstrated the role of apoB/apoA-I ratio as a strong risk factor for cardiovascular diseases. To determine the concentration of cord blood lipoproteins and apolipoproteins as well as their correlation with birth weight. This cross-sectional study was conducted in a teaching institution in central India. Healthy full-term newborns, born out of normal vaginal deliveries, were recruited. Cases include term small for gestational age (SGA) babies while term appropriate for gestational age (AGA) babies were taken as controls. Their umbilical venous blood was collected and sent for biochemical analysis. Out of 126 healthy newborns, 66 were cases and 60 were controls. Mean values of serum triglyceride (141.56±69.67 mg/dl vs. 113.67±33.38 mg/dl; p < 0.006; 95% CI = 8.31 to 47.46) and serum apo-B/apo-A-1 ratio (0.67±0.28 vs. 0.55±0.20; p < 0.007; 95% CI = 0.033 to 0.206) were significantly high and that of serum high density cholesterol (35.84±10.42 mg/dl vs. 40.73±11.70 mg/dl; p < 0.014; 95% CI = -8.79 to -0.98) and Apo-A1 [87.59±12.44 mg/dl vs. 101.87±35.07 mg/dl; p = 0.002; 95% CI = -23.39 to -5.16) were significantly low in SGA newborns. Serum cholesterol, very low-density cholesterol rlow-density cholesterol rand Apo-B did not show any significant difference. Among SGA newborns significant negative correlation was seen between birth weight and apo-B/apo-A1 and serum triglyceride, while birth weight and serum apo-A1 level showed significant positive correlation. There was no statistically significant correlation between birth weight and other parameters. These findings further support the association of prenatal factors with lipid profile rand can serve as starting point for studying lipid transport system changes during early life in Indian population.

Alzheimer Disease Signature Neurodegeneration and APOE Genotype in Mild Cognitive Impairment With Suspected Non–Alzheimer Disease Pathophysiology

ImportanceThere are conflicting results claiming that Alzheimer disease signature neurodegeneration may be more, less, or similarly advanced in individuals with β-amyloid peptide (Aβ)–negative (Aβ−) suspected non–Alzheimer disease pathophysiology (SNAP) than in Aβ-positive (Aβ+) counterparts.ObjectiveTo examine patterns of neurodegeneration in individuals with SNAP compared with their Aβ+ counterparts.Design, Setting, and ParticipantsA longitudinal cohort study was conducted among individuals with mild cognitive impairment (MCI) and cognitively normal individuals receiving care at Alzheimer’s Disease Neuroimaging Initiative sites in the United States and Canada for a mean follow-up period of 30.5 months from August 1, 2005, to June 30, 2015. Several neurodegeneration biomarkers and longitudinal cognitive function were compared between patients with distinct SNAP (Aβ− and neurodegeneration-positive [Aβ−N+]) subtypes and their Aβ+N+ counterparts. Main Outcomes and MeasuresParticipants were classified according to the results of their florbetapir F-18 (Aβ) positron emission tomography and their Alzheimer disease–associated neurodegeneration status (temporoparietal glucose metabolism determined by fluorodeoxyglucose F 18 [FDG]–labeled positron emission tomography and/or hippocampal volume [HV] determined by magnetic resonance imaging: participants with subthreshold HV values were regarded as exhibiting hippocampal volume atrophy [HV+], while subthreshold mean FDG values were considered as FDG hypometabolism [FDG+]).ResultsThe study comprised 265 cognitively normal individuals (135 women and 130 men; mean [SD] age, 75.5 [6.7] years) and 522 patients with MCI (225 women and 297 men; mean [SD] age, 72.6 [7.8] years). A total of 469 individuals with MCI had data on neurodegeneration biomarkers; of these patients, 107 were Aβ−N+ (22.8%; 63 FDG+, 82 HV+, and 38 FDG+HV+) and 187 were Aβ+N+ (39.9%; 135 FDG+, 147 HV+, and 95 FDG+HV+ cases). A total of 209 cognitively normal participants had data on neurodegeneration biomarkers; of these, 52 were Aβ−N+ (24.9%; 30 FDG+, 33 HV+, and 11 FDG+HV+) and 37 were Aβ+N+ (17.7%; 22 FDG+, 26 HV+, and 11 FDG+HV+). Compared with their Aβ+ counterparts, all patients with MCI SNAP subtypes displayed better preservation of temporoparietal FDG metabolism (mean [SD] FDG: Aβ–N+, 1.25 [0.11] vs Aβ+N+, 1.19 [0.11]), less severe atrophy of the lateral temporal lobe, and lower mean (SD) cerebrospinal fluid levels of tau (59.2 [32.8] vs 111.3 [56.4]). In MCI with SNAP, sustained glucose metabolism and gray matter volume were associated with disproportionately low APOE ε4 (Aβ–N+, 18.7% vs Aβ+N+, 70.6%) and disproportionately high APOE ε2 (18.7% vs 4.8%) carrier prevalence. Slower cognitive decline and lower rates of progression to Alzheimer disease (Aβ–N+, 6.5% vs Aβ+N+, 32.6%) were also seen in patients with MCI with SNAP subtypes compared with their Aβ+ counterparts. In cognitively normal individuals, neurodegeneration biomarkers did not differ between Aβ−N+ and Aβ+N+ cases.Conclusions and RelevanceIn MCI with SNAP, low APOE ε4 and high APOE ε2 carrier prevalence may account for differences in neurodegeneration patterns between Aβ−N+ and Aβ+N+ cases independent from the neuroimaging biomarker modality used to define neurodegeneration associated with Alzheimer disease.

Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals.

Low serum apolipoprotein (Apo) A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL) and low-density lipoprotein (LDL). However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups). These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations (r between 0.05 and 0.25) were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI), and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages) was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

Eicosapentaenoic acid-enriched phospholipids improve atherosclerosis by mediating cholesterol metabolism

Dietary fish oil could prevent and treat atherosclerosis by improving lipid metabolism; in apolipoprotein E-deficient (apoE−/−) mice, it was ineffective at lowering serum lipid levels but still showed anti-atherosclerosis action. To date, no direct evidence has comparatively evaluated the effect of docosahexaenoic acid-enriched and eicosapentaenoic acid-enriched phospholipids (DHA-PL and EPA-PL) on atherosclerosis in apoE−/− mice. The present study suggested that both 1% dietary DHA-PL and EPA-PL could significantly reduce atherosclerotic lesions (37.4% and 53.4%, respectively) in high fat diet apoE−/− mice. EPA-PL significantly decreased serum and hepatic lipid levels, by mediating mRNA and protein levels of genes related to hepatic cholesterol metabolism, whereas DHA-PL was ineffective. In the suppression of aortic proinflammatory cytokines, DHA-PL was superior to EPA-PL at reducing TNF-α, IL-6, and IL-1β transcription. In conclusion, the action of DHA-PL was simply anti-inflammatory, and that of EPA-PL was mainly the improvement of lipid metabolism in the amelioration of atherosclerosis.

RAGE deficiency alleviates aortic valve calcification in ApoE−/− mice via the inhibition of endoplasmic reticulum stress

Receptor for advanced glycation end products (RAGE) and endoplasmic reticulum (ER) stress have been shown to be involved in calcific aortic valve disease (CAVD). However, the association between RAGE and ER stress remains unknown in the pathogenesis of CAVD. The current study aims to test the hypothesis that RAGE deficiency alleviates aortic valve calcification via the inhibition of ER stress. Up-regulation of RAGE and ER stress markers in calcified human aortic valves were confirmed by immunoblotting. Aortic valve calcification was evaluated in atherosclerotic prone ApoE−/− mice or in mice with dual deficiencies of ApoE and RAGE (ApoE−/−RAGE−/−) fed with high cholesterol diet for 24weeks. Echocardiography and histological examination show that genetic deficiency of RAGE attenuates aortic valve calcification in ApoE−/− mice. Meanwhile, RAGE deficiency inhibited the osteogenic signaling and ER stress activation as well as suppressed macrophage infiltration in vivo. Cultured human aortic valve interstitial cells (AVICs) were treated with high molecular group box 1 protein (HMGB1) as in vitro model. We found that HMGB1 induced osteoblastic differentiation and calcification through RAGE/ER stress. Furthermore, Sox9 up-regulation and intranuclear translocation mediated the pro-osteogenic effect of HMGB1 on AVICs. RAGE or ER stress knockdown reduced the up-regulation of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in human AVICs exposed to HMGB1.These novel findings demonstrate that RAGE deficiency protects against aortic valve calcification in high cholesterol diet-fed ApoE−/− mice via inhibition of ER stress. HMGB1 induces AVIC osteoblastic differentiation and calcification through RAGE/ER stress/Sox9 pathway.

Serum levels of apolipoprotein E correlates with disease progression and poor prognosis in breast cancer.

ApoE has been reported to be associated with tumorigenesis and tumor progression. In this study, we explored the potential diagnostic and prognostic role of serum ApoE in breast cancer patients. Subject cohorts consisted of 152 normal healthy controls female and 257 breast cancer cases. Serum levels of ApoE were determined with turbidimetric immunoassay. The serum levels of ApoE were significantly elevated in breast cancer patients compared with normal healthy controls (45.82±13.96mg/L vs. 33.61±6.44mg/L, respectively, P<0.0001) and also significantly associated with TNM stage and lymph nodes status (all P<0.05). Area under receiver operating characteristic curve for serum ApoE discriminate breast cancer patients from controls was 0.786 with specificity of 0.974 and sensitivity of 0.541, the cut-off value of ApoE was 43.15mg/L. Kaplan-Meier log rank analysis showed that the high serum ApoE group (serum ApoE≥43.15mg/L) had a poorer progression-free survival and overall survival compared with low serum ApoE group (serum ApoE<43.15mg/L) (all P<0.05). In addition, univariate and multivariate Cox regression analysis displayed serum ApoE as an independent risk factor of breast cancer patients prognosis (all P<0.05). Serum ApoE played a role as serological biomarkers that indicated diagnostic and prognostic evaluation in breast cancer patients.

Factors influencing atherogenic indices in type 2 diabetic women in northwestern Algeria

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; &lt;span lang="EN-GB"&gt;Type 2 diabetic women are at higher risk of developing atherogenic dyslipidemia. The major possible risk factors are obesity, abdominal fat accumulation and poor glycaemic control. However, menopause-related changes could be another determinant. The aim of this study was to evaluate the interrelationships of these risk factors and their independent effects on atherogenic indices in type 2 diabetes women&lt;/span&gt;.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; &lt;span lang="EN-GB"&gt;A prospective, cross-sectional study, which includes 160 women agreed to participate in this study. Anthropometrics, biochemical parameters and blood pressure were measured. Atherogenic indices - total cholesterol-to-high-density lipoprotein cholesterol ratio (TC/HDL) and apolipoprotein (apo) B-to-apo A1 ratio, were calculated. Individual risk factors were examined in relationship to these atherogenic indices using correlation tests and logistic regression&lt;/span&gt;&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;span lang="EN-IN"&gt; &lt;/span&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; &lt;span lang="EN-GB"&gt;23.12% of the participants were normal weight and 76.87% were overweight/obese. The overall mean age was 57.70±11.16 years. Diabetes duration (˃5years), anthropometric parameters, poor glycaemic control, high apo B and high level of low-density lipoprotein (LDL) were found to be significant determinants of atherogenic indices changes. &lt;/span&gt;&lt;span lang="EN-GB"&gt;The TC/HDL ratio was weakly associated with both BMI and waist circumference. However, the apo B/apo A1 ratio provided positive correlations with anthropometric parameters, especially with waist circumference (&lt;em&gt;p&lt;/em&gt;=0.185, r=0.108, r&lt;sup&gt;2&lt;/sup&gt;=0.012), and this, in both pre and post-menopausal type 2 diabetic women&lt;/span&gt;.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; &lt;span lang="EN-GB"&gt;The atherogenic risk, estimated by TC/HDL and apo B/apo A1 ratios, becomes more severe with higher anthropometric parameters (BMI and waist circumference), diabetes duration and poor glycaemic control in type 2 diabetes women and this during both premenopausal and postmenopausal periods&lt;/span&gt;&lt;span lang="EN-IN"&gt;. &lt;/span&gt;&lt;/p&gt;

Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection.

As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p=0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.

Concurrence of High Fat Diet and APOE Gene Induces Allele Specific Metabolic and Mental Stress Changes in a Mouse Model of Alzheimer's Disease.

Aging is the main risk factor for neurodegenerative diseases, including Alzheimer’s disease (AD). However, evidence indicates that the pathological process begins long before actual cognitive or pathological symptoms are apparent. The long asymptomatic phase and complex integration between genetic, environmental and metabolic factors make it one of the most challenging diseases to understand and cure. In the present study, we asked whether an environmental factor such as high-fat (HF) diet would synergize with a genetic factor to affect the metabolic and cognitive state in the Apolipoprotein E (ApoE4) mouse model of AD. Our data suggest that a HF diet induces diabetes mellitus (DM)-like metabolism in ApoE4 mice, as well as changes in β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protein levels between the two ApoE strains. Furthermore, HF diet induces anxiety in this AD mouse model. Our results suggest that young ApoE4 carriers are prone to psychological stress and metabolic abnormalities related to AD, which can easily be triggered via HF nutrition.

Neglected but Important Role of Apolipoprotein E Exchange in Hepatitis C Virus Infection

In this study, a neglected but important role of apoE exchange in HCV LVP infectivity after virus assembly and release was identified. The data indicated that apoE expression level in uninfected cells is important for high permissiveness to HCV infection. Secreted apoE-associated lipoprotein specifically enhances infection of HCV LVPs. apoE exchange between HCV LVP and lipoproteins is important to maintain an adequate apoE level on LVPs for their efficient attachment to cell surface. These data defined for the first time an extracellular role of exchangeable apoE in HCV infection and suggested that exchangeable apolipoproteins reach a natural equilibrium between HCV LVPs and lipoprotein particles, which provides a new perspective to the understanding of the heterogeneity of HCV LVPs in composition.

Hepatocyte vitamin D receptor regulates lipid metabolism and mediates experimental diet-induced steatosis

The pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD) is still incompletely understood. Several nuclear receptors play a role in liver lipid metabolism and can promote hepatosteatosis, but the possible role of vitamin D receptor (VDR) in NAFLD has not been investigated. The expression of liver VDR was investigated in apolipoprotein E knockout (apoE(-/-)) mice on a high fat diet, in wild-type mice on methionine and choline deficient diet and in NAFLD patients with hepatosteatosis and non-alcoholic steatohepatitis. The relevance of VDR was assessed in apoE(-/-) mice by deletion of VDR or paricalcitol treatment and in human HepG2 cells by VDR transfection or silencing. The role of VDR in fibrosis was also determined in VDR knockout mice (VDR(-/-)) treated with thioacetamide. Expression of liver VDR was markedly induced in two mouse models of NAFLD, as well as in patients with hepatosteatosis, but decreased in non-alcoholic steatohepatitis. VDR deletion in high fat diet-fed apoE(-/-) mice protected against fatty liver, dyslipidemia and insulin resistance, and caused a decrease in taurine-conjugated bile acids, but did not influence fibrosis by thioacetamide. apoE(-/-)VDR(-/-) mouse livers showed decreased gene expression of CD36, DGAT2, C/EBPα and FGF21, and increased expression of PNPLA2, LIPIN1 and PGC1α. Treatment of apoE(-/-) mice on high fat diet with paricalcitol had modest opposite effects on steatosis and gene expression. Finally, this set of genes showed concordant responses when VDR was overexpressed or silenced in HepG2 cells. Induced hepatocyte VDR in NAFLD regulates key hepatic lipid metabolism genes and promotes high fat diet-associated liver steatosis. Therapeutic inhibition of liver VDR may reverse steatosis in early NAFLD. The amount of vitamin D receptor is induced early in the livers of mice and humans when they develop non-alcoholic fatty liver disease. If the gene for the vitamin D receptor is deleted, hepatic lipid metabolism changes and mice do not accumulate fat in the liver. We conclude that the vitamin D receptor can contribute to the fatty liver disease promoted by a high fat diet.