Levels Of Apolipoprotein Research Articles

Abstract P176: Associations of Gestational Lipids and Apolipoproteins With Pregnancy Outcomes: The Hyperglycemia and Adverse Pregnancy Outcome Study

Introduction: Gestational hyperlipidemia has traditionally been considered physiologic and benign, but the significance of inter-individual variation in lipid levels for maternal-fetal health are poorly understood. We examined associations of gestational lipids and apolipoproteins with adverse obstetric and neonatal outcomes. Methods: Data from the Hyperglycemia and Adverse Pregnancy Outcome Study were analyzed, including 1,813 mother-child dyads from 9 field centers in 6 countries: US (25%), Barbados (24%), UK (20%), China (16%), Thailand (8%), and Canada (7%). Fasting lipids and apolipoproteins were directly measured at a mean of 28 (range 23-34) weeks’ gestation. Cord blood was collected at delivery, neonatal anthropometrics were measured within 72 hours, and medical records were abstracted for obstetric outcomes. Logistic regression was utilized to test associations of lipids and apolipoproteins (per +1 SD; log-transformed if skewed) with pregnancy outcomes, adjusted for center, demographics, and maternal covariates such as BMI, blood pressure, and glycemia. Results: See Table for lipid and apolipoprotein levels in pregnant mothers. In fully adjusted models ( Table ), 1 SD higher log-triglycerides (i.e., ~2.7-fold higher triglyceride level) in late pregnancy was significantly associated with higher odds for preeclampsia (OR 1.53 [95% CI, 1.15-2.05]), large for gestational age infant (1.42 [1.21-1.67]), and infant insulin sensitivity <10 th percentile (1.25 [1.03-1.50]), but not with unplanned primary cesarean section or infant sum of skinfolds >90 th percentile. There were no significant associations of maternal HDL-C, LDL-C, or log-ApoB/A1 ratio with any outcome. Conclusion: Triglyceride levels in the latter half of pregnancy were uniquely associated with both maternal risks (preeclampsia) and neonatal risks (large for gestational age and insulin resistance), even after adjustment for maternal BMI, blood pressure, and glycemia.

Abstract P178: Relationship of Apolipoproteins With Subclinical Cardiovascular Risk in Youth

Introduction: Apolipoproteins are key regulators of cholesterol transport and clearance with each apolipoprotein having a specific protective or atherogenic role. The relationship between subclinical cardiovascular risk and each of the apolipoproteins in the pediatric population is insufficiently described within the literature. Therefore, the purpose of this study was to examine the association of apolipoproteins with measures of vascular structure and function in pediatric population. Hypothesis: We hypothesized apolipoprotein AI, AII, and CII would demonstrate a positive association, and apolipoprotein B, B/AI ratio, CIII, CIII/CII ratio, and E a negative association with carotid intima-media thickness (cIMT) and carotid-radial pulse wave velocity (PWV). Methods: A cross-sectional study of 338 children and adolescents (160 males, 178 females) aged 8-21 years (mean age 13.0±2.8 years) with a range of adiposities from normal body weight to severe obesity (mean BMI 26.8±8.9 kg/m 2 ). Apolipoproteins (AI, AII, B, CII, CIII, and E) were measured via human apolipoprotein magnetic bead panel (Millipore, MA, USA). Ultrasound imaging of the carotid artery was used to measure cIMT. PWV, a measure of arterial stiffness, was assessed via applanation tonometry (SphygmoCor TM ). Total body fat percent (BF%) was measured using dual X-ray absorptiometry. Linear regression models were adjusted for Tanner stage, sex, and race with further adjustments for BF%. Data are presented as mean [95% CI] with Holms-adjusted p-values to account for multiple testing. All apolipoprotein ratios were scaled to 0.1 μg/mL. Methods: There were significant positive associations between PWV and apolipoproteins: AII (0.036 m/sec per 10 μg/mL [0.017, 0.056], p = 0.010), E (0.158 m/sec per 10 μg/mL [0.08, 0.235], p = 0.002), and CIII/CII ratio (0.033 [0.014, 0.052], p = 0.019). After adding BF% to the models, PWV remained positively associated with higher levels of apolipoproteins: AII (0.036 m/sec per 10 μg/mL [0.016, 0.055], p = 0.012), E (0.161 m/sec per 10 μg/mL [0.082, 0.239], p = 0.002), and CIII/CII ratio (0.033 [0.014, 0.052], p = 0.02). Before accounting for multiple testing, apolipoprotein CIII/CII ratio was positively associated with cIMT (0.001 [0, 0.003], p = 0.033), but failed to maintain significance after p-value correction. Otherwise, there were no significant associations between any apolipoprotein and cIMT in the presence or absence of BF%. Conclusions: These findings suggest higher levels of apolipoprotein AII, E, and CIII/CII ratio are associated with higher arterial stiffness (PWV) in pediatrics, both in the presence and absence of excess body fat. Apolipoproteins, specifically AII, E, and CIII/CII ratio, may exert their effects on vascular function (PWV) before altering vascular structure (cIMT), which is congruent with the chronological pathophysiology of atherosclerosis.

Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology

ObjectivesThe mechanisms leading to neurodegeneration in Alzheimer's disease (AD) may involve oxidative stress and neuroinflammation. Ceruloplasmin (Cp) is a circulating protein that intersects both these pathways, since its expression is increased during the acute phase response, and the protein acts to lower pro-oxidant iron in cells. Since the role of Cp in AD, and its potential for use as a biomarker is not established, we investigated CSF Cp and its association with longitudinal outcome measures related to AD. MethodsThis was an observational study of 268 people from the Alzheimer's Disease Neuroimaging (ADNI) cohort. Subjects were classified clinically as having AD, mild cognitive impairment (MCI) or were cognitively normal (CN), and were also classified as being positive for β-amyloid using established thresholds in the CSF t-tau/Aβ42 ratio. Subjects underwent cognitive tests and MRI studies every 6 months for 2 years, then yearly thereafter for up to 6 years. ResultsAt baseline, CSF Cp was not associated with clinical or pathological diagnosis, but we found an unexpected association between CSF Cp and levels of CSF apolipoprotein E. In longitudinal analysis, high level of CSF Cp was associated with accelerated cognitive decline (as assessed by ADAS-Cog, CDR-SB, and MMSE) and ventricular volume enlargement in people classified as MCI and who had underlying β-amyloid pathology. ConclusionThese results raise new questions into the role of Cp in neuroinflammation, oxidative stress, and APOE pathways involved in AD, and reveal the potential for this protein to be used as a biomarker in disease prognostication.

Analysis on the polymorphisms of site RS4977574, and RS1333045 in region 9p21 and the susceptibility of coronary heart disease in Chinese population

BackgroundRs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population.MethodsBlood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software.ResultsAssociation analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher’s exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype.ConclusionsThe present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure

High-density lipoprotein cholesterol (HDL-C) levels are reduced in patients with chronic liver disease and inversely correlate with disease severity. During acute conditions such as sepsis, HDL-C levels decrease rapidly and HDL particles undergo profound changes in their composition and function. We aimed to determine whether indices of HDL quantity and quality associate with progression and survival in patients with advanced liver disease. HDL-related biomarkers were studied in 508 patients with compensated or decompensated cirrhosis (including acute-on-chronic liver failure [ACLF]) and 40 age- and gender-matched controls. Specifically, we studied levels of HDL-C, its subclasses HDL2-C and HDL3-C, and apolipoprotein A1 (apoA-I), as well as HDL cholesterol efflux capacity as a metric of HDL functionality. Baseline levels of HDL-C and apoA-I were significantly lower in patients with stable cirrhosis compared to controls and were further decreased in patients with acute decompensation (AD) and ACLF. In stable cirrhosis (n= 228), both HDL-C and apoA-I predicted the development of liver-related complications independently of model for end-stage liver disease (MELD) score.In patients with AD, with or without ACLF (n= 280), both HDL-C and apoA-I were MELD-independent predictors of 90-day mortality. On ROC analysis, both HDL-C and apoA-I had high diagnostic accuracy for 90-day mortality in patients with AD (AUROCs of 0.79 and 0.80, respectively, similar to that of MELD 0.81). On Kaplan-Meier analysis, HDL-C <17 mg/dl and apoA-I <50 mg/dl indicated poor short-term survival. The prognostic accuracy of HDL-C was validated in a large external validation cohort of 985 patients with portal hypertension due to advanced chronic liver disease (AUROCs HDL-C: 0.81 vs. MELD: 0.77). HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure. People who suffer from cirrhosis (scarring of the liver) have low levels of cholesterol carried by high-density lipoproteins (HDL-C). These alterations are connected to inflammation, which is a problem in severe liver disease. Herein, we show that reduced levels of HDL-C and apolipoprotein A-I (apoA-I, the main protein carried by HDL) are closely linked to the severity of liver failure, its complications and survival. Both HDL-C and apoA-I can be easily measured in clinical laboratories and are as good as currently used prognostic scores calculated from several laboratory values by complex formulas.

Generation of new hepatocyte-like in vitro models better resembling human lipid metabolism

In contrast to human hepatocytes in vivo, which solely express acyl-coenzyme A:cholesterol acyltransferase (ACAT) 2, both ACAT1 and ACAT2 (encoded by SOAT1 and SOAT2) are expressed in primary human hepatocytes and in human hepatoma cell lines. Here, we aimed to create hepatocyte-like cells expressing the ACAT2, but not the ACAT1, protein to generate a model that – at least in this regard – resembles the human condition in vivo and to assess the effects on lipid metabolism. Using the Clustered Regularly Interspaced Short Palindromic Repeats technology, we knocked out SOAT1 in HepG2 and Huh7.5 cells. The wild type and SOAT2-only-cells were cultured with fetal bovine or human serum and the effects on lipoprotein and lipid metabolism were studied. In SOAT2-only-HepG2 cells, increased levels of cholesterol, triglycerides, apolipoprotein B and lipoprotein(a) in the cell media were detected; this was likely dependent of the increased expression of key genes involved in lipid metabolism (e.g. MTP, APOB, HMGCR, LDLR, ACACA, and DGAT2). Opposite effects were observed in SOAT2-only-Huh7.5 cells. Our study shows that the expression of SOAT1 in hepatocyte-like cells contributes to the distorted phenotype observed in HepG2 and Huh7.5 cells. As not only parameters of lipoprotein and lipid metabolism but also some markers of differentiation/maturation increase in the SOAT2-only-HepG2 cells cultured with HS, this cellular model represent an improved model for studies of lipid metabolism.

Apolipoproteins B and A1 in Ischemic Stroke Subtypes

Introduction: Elevated serum apolipoprotein B and the apolipoprotein B/A1 ratio have been associated with ischemic stroke and intracranial atherosclerotic disease. We sought to assess the relationship between serum levels of apolipoprotein B, apolipoprotein A1, and the apolipoprotein B/A1 ratio with ischemic stroke subtypes and large artery atherosclerosis location. Materials and Methods: We evaluated serum apolipoprotein B and apolipoprotein A1 levels in consecutive, statin-naïve, adult ischemic stroke patients admitted to an academic medical center in southern India. We evaluated for differences in the mean serum levels of apolipoprotein B, apolipoprotein A1, and the apolipoprotein B/A1 ratio between patients with ischemic stroke attributed to intracranial atherosclerotic disease, extracranial atherosclerotic disease, small vessel disease, and cardioembolism. In secondary analysis, we assessed for differences in these serum apolipoproteins between patients with moderate-severe intracranial atherosclerotic disease and extracranial atherosclerotic disease, irrespective of ischemic stroke subtype. Results: Among the 156 ischemic stroke patients enrolled in this study, there were no significant differences in serum levels of apolipoprotein B, apolipoprotein A1, and the apolipoprotein B/A1 ratio between patients with distinct ischemic stroke subtypes. No significant differences were found in serum levels of apolipoprotein B, A1 and the apolipoprotein B/A1 ratio between patients with moderate-severe intracranial atherosclerotic disease and moderate-severe extracranial atherosclerotic disease. Discussion: Serum levels of apolipoprotein B and A1 did not differ between ischemic stroke subtypes. Additional studies are needed to validate our findings and to better understand the relationship between serum apolipoproteins and stroke.

STUDIES ON APOLIPOPROTEINS (APO A1 &amp; APO B) AND LIPOPROTEIN (A) ALONG WITH LIPID PROFILE IN THE PATIENTS OF TYPE II DIABETES MELLITUS AND METABOLIC SYNDROME

Patients with Type II diabetes mellitus or the metabolic syndrome have unique dyslipidemia characterized by hypertriglyceridemia; elevated blood levels of apolipoprotein B; small, dense low-density lipoprotein (LDL) cholesterol; and low levels of high-density lipoprotein (HDL) cholesterol. Treatment of dyslipidemia associated with these disorders should focus on correcting the abnormal lipoprotein levels as well as LDL and HDL heterogeneity. Statins and fibrates are useful for treating elevated LDL in patients with and without diabetes or the metabolic syndrome. There are few researches on Apolipoprotein A and Apolipoprotein B, Lipoprotein (a) in India, in comparison to foreign countries. So this study is aimed to evaluate Apo lipoproteins (Apo A1 &amp; Apo B) and Lipoprotein (a) levels along with Lipid profile in Type II Diabetes Mellitus and in patients with Metabolic Syndrome which can be correlated with the risk of cardiovascular disease.&#x0D; Conclusion: Apo lipoprotein A1, Apolipoprotein B and Lipoprotein (a) can be important marker for the risk developing of heart disease. Statistical relationships between LDL and HDL and their respective Apo lipoproteins, Apo B and Apo A-1, in diabetic and metabolic syndrome can be established.&#x0D; Keywords: Lipid profile, Type II Diabetes Mellitus, Apo lipoproteins (Apo A &amp; Apo B), Lipoprotein (a) and Metabolic Syndrome.

Comparative and correlation study of biochemical substances in serum and urine of lysosomal disease patients

There is increasing evidence that serum lipids and apolipoproteins may be associated with multiple sclerosis (MS) clinical course.To investigate the associations between serum lipids, apolipoproteins, body mass index and relapse in MS.A prospective cohort of 141 participants with relapsing–remitting MS was followed from 2002 to 2005. Serum lipid and apolipoprotein levels were measured biannually, and body mass index at baseline. The association with hazard of relapse was assessed using survival analysis.Neither body mass index nor any of the lipid-related measures were associated with the hazard of relapse.Serum lipid profile and body mass index are not associated with the hazard of relapse in MS.

Lipid profiling in maternal and fetal circulations in preeclampsia and fetal growth restriction-a prospective case control observational study

BackgroundWhile many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglycerides (TG), Apolipoprotein A1, Apolipoprotein B and their ratios TC/HDL and ApoB/ApoA1 in the maternal and fetal circulations of normal pregnancy, preeclampsia (PE), fetal growth restriction (FGR) and PE + FGR.MethodsA prospective cross-sectional case control study was conducted measuring maternal and fetal lipid levels by enzymatic analysis and immune-turbidimetric enzymatic assays. FGR was defined by elevated umbilical artery Doppler resistance in association with estimated fetal weight < 10%. Kruskal Wallis non-parametric analysis of variance was used to test for homogeneity across the clinical groups for each of the variables, Mann-Whitney tests for pairwise comparisons and Spearman rank correlation were used to quantify gestational age-related changes.Results(1) TG levels were elevated in maternal PE and cord blood PE + FGR groups compared to normal pregnancies. (2) A statistically significant elevation of fetal ApoB levels was observed in PE, FGR and PE + FGR compared to normal pregnancies. Apolipoprotein levels A1 and B were not different between maternal groups. (3) TC, HDL, LDL and TC/HDL levels did not show any significant gestational variation or between clinical groups in the maternal or fetal circulation.ConclusionsElevation in maternal TG levels may have a role in the pathogenesis of PE. The implications of elevated maternal and fetal TG levels and elevated fetal Apolipoprotein B levels deserves further exploration of their role in long term cardiovascular risk in the mother as well as the offspring.

HDL cholesterol efflux capacity is related to disease activity in psoriatic arthritis patients.

Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein (HDL) cholesterol to accept cholesterol from macrophages. CEC is linked to cardiovascular events in the general population, and it has been shown to be disrupted in inflammatory states. The aim of this study was to establish whether CEC is impaired in PsA patients and if this could be explained by disease-related features like disease activity. Case-control study that encompassed 105 individuals: 52 PsA patients and 53 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Disease activity in patients with PsA was measured using the Disease Activity Index for Psoriatic Arthritis (DAPSA). Multivariate analysis was performed to study the differences between CEC in patients and controls, and the relation of CEC with PsA activity-related data and lipid profile. Total cholesterol, apolipoprotein A1, and LDL cholesterol serum levels were downregulated in PsA patients. CEC did not differ between controls and patients (17 ± 10 vs. 18 ± 2%, p = 0.15) after adjusting for traditional cardiovascular risk factors or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, were not related to CEC. After multivariate regression analysis, the DAPSA score was inversely and independently associated with CEC (beta coefficient - 0.75 [95%CI - 1.39-- 0.11] %, p = 0.023). CEC is inversely associated with disease activity in PSA patients, reinforcing the role of disease activity as a key factor in the development of accelerated atherosclerosis in these patients.Key Points• Cholesterol efflux capacity is linked to cardiovascular events in the general population.• In patients with psoriatic arthritis, cholesterol efflux capacity is inversely associated with disease activity (beta coefficient - 0.75[95% CI - 1.39-- 0.11] %, p = 0.023).• This finding reinforces the role of disease activity as a key factor in increasing cardiovascular risk in psoriatic arthritis patients.

Dipeptidyl peptidase-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels in patients with type 2 diabetes: A randomized controlled trial.

Type 2 diabetes and dyslipidemia are diseases that collectively increase the risk of patients developing cardiovascular complications. Several incretin-based drugs are reported to improve lipid metabolism, and one of these medications, anagliptin, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been shown to decrease serum triglyceride and low-density lipoproteins cholesterol. This study aimed to conduct an investigation into the effects of anagliptin on serum lipid profiles. This multicenter, open-label, randomized (1:1), parallel group study was designed to evaluate the effects of anagliptin on serum lipid profiles (triglycerides, lipoproteins, apolipoproteins, and cholesterol fractions). The study involved 24 patients with type 2 diabetes at two participating hospitals for a period of 24 weeks. Patients were randomly assigned to the anagliptin (n = 12) or control (n = 12) groups. Patients in the anagliptin group were treated with 200 mg of the drug twice daily. Patients in the control group did not receive anagliptin, but continued with their previous treatment schedules. Lipid metabolism was examined under fasting conditions at baseline and 24 weeks. Patients treated with anagliptin for 24 weeks exhibited significantly reduced levels of serum apolipoprotein B-48, a marker for lipid transport from the intestine, compared with the control group patients (P < 0.05). After 24 weeks of treatment, serum adiponectin levels were significantly raised, whereas glycated hemoglobin (HbA1c) levels were significantly lower compared with the baseline in the anagliptin group (P < 0.05), but not in the control group. This study showed that the DPP-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels, suggesting that this drug may have beneficial effects on lipid metabolism possibly mediated by the inhibition of intestinal lipid transport.

Plant-Based Diet Reverses Vascular Endothelial Dysfunction in Patients with Peripheral Arterial Disease

OBJECtIVE: Peripheral arterial disease (PAD) is characterized by impaired arterial circulation to the extremities caused in part by atherosclerosis. This study examined the effect of a plant-based diet (PBD) on vascular function in PAD patients.METHODs: Patients with PaD were randomized to plant-based dietary intervention (PBD group, n = 24) or no specific dietary advice (control group, n = 28). Biochemical parameters, including lipid profile and inflammatory biomarkers, and nitric oxide were measured at baseline and 4 months after dietary intervention. Vascular function including brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness(IMT), carotid-femoral pulse wave velocity (PWV), and brachial-ankle PWV were measured at baseline and 4 months after dietary intervention.RESULTS: Biochemical parameters were similar at baseline between the 2 groups. There was no change in any of the biochemical parameters in the control group at 4 months. However, patients in the PBD group had a significant improvement in lipid profile, including total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein a1 (APO-A1) levels. Greater nitric oxide and reduced high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were found in the PBD group at 4 months, whereas there were no changes in the control group. at baseline, FMD was similar between the 2 groups. after 4 months, PBD participants showed significant endothelial function improvement in FMD response and arterial stiffness response, with increased carotid-femoral and brachial-ankle PWV compared to the control group.&#x0D; CONCLUSIONS: A plant-based diet improves vascular endothelial function in PaD patients following 4 months of dietary intervention. This dietary intervention can result in decreased serum cholesterol and inflammatory biomarkers, which may further enhance vascular endothelial function.&#x0D; KEYWORDS: Plant-based diet; Vascular endothelial function; Flow-mediated dilation; Brachial artery reactivity test

Murine Surf4 is essential for early embryonic development.

Newly synthesized proteins co-translationally inserted into the endoplasmic reticulum (ER) lumen may be recruited into anterograde transport vesicles by their association with specific cargo receptors. We recently identified a role for the cargo receptor SURF4 in facilitating the secretion of PCSK9 in cultured cells. To examine the function of SURF4 in vivo, we used CRISPR/Cas9-mediated gene editing to generate mice with germline loss-of-function mutations in Surf4. Heterozygous Surf4+/- mice exhibit grossly normal appearance, behavior, body weight, fecundity, and organ development, with no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol, and a detectable accumulation of intrahepatic apoliprotein B. Homozygous Surf4-/- mice exhibit embryonic lethality, with complete loss of all Surf4-/- offspring between embryonic days 3.5 and 9.5. In contrast to the milder murine phenotypes associated with deficiency of known SURF4 cargoes, the embryonic lethality of Surf4-/- mice implies the existence of additional SURF4 cargoes or functions that are essential for murine early embryonic development.

Carnosic Acid Reverses the Inhibition of ApoE4 on Cell Surface Level of ApoER2 and Reelin Signaling Pathway.

The cell surface level of apolipoprotein E receptor 2 (ApoER2) increases by cyclic transport of ApoER2 and then activates Reelin signaling pathway to exert neuroprotective function in AD. ApoER2 ligand Apolipoprotein E4 (ApoE4) inhibits the recycling of ApoER2 to the cell surface rendering neurons unresponsive to Reelin. Carnosic acid (CA) is proven to possess neuroprotective and neurotrophic functions in Alzheimer's disease (AD) mouse model. However, there are few reports about how ApoE4 impairs the recycling of ApoER2 and if CA can affect the cyclic transport of ApoER2. In this study, we demonstrated that ApoE4 attenuates the binding of sorting nexin 17 (SNX17) to ApoER2 and inhibits the recycling of ApoER2, resulting in decreased cell surface level of ApoER2. Further, we found that CA enhances the binding of SNX17 to ApoER2, counteracts the negative effects of ApoE4 on the cell surface level of ApoER2 to reverse the ApoE4-induced reduction in Reelin signaling activation by increasing the phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) and cAMP-response element-binding protein (CREB) and the expression of Gria2. Thus, CA promotes neurite growth inhibited by ApoE4. Our work suggests that CA may be a potential approach to attenuate the risk of ApoE4-associated AD.

Self-reported Morisky Eight-item Medication Adherence Scale for Statins Concords with the Pill Count Method and Correlates with Serum Lipid Profile Parameters and Serum HMGCoA Reductase Levels.

BackgroundIt is imperative that non-compliance with statins be identified and addressed to maximize their clinical benefits. Patient self-reporting methods are convenient to apply in clinical practice but need to be validated.ObjectiveWe studied the concordance of a patient self-report method, Morisky eight-item medication adherence scale (MMAS)), with the pill count method in measuring adherence with statins and their correlation with extended lipid profile parameters and serum hydroxyl-methylglutaryl coenzyme A reductase (HMGCoA-R) enzyme levels.MethodsMMAS and the pill count method were used to measure the adherence with statins in patients on statins for any duration. Patients were subjected to an estimation of extended lipid profile and serum HMGCoA-R levels at the end of three months follow-up.ResultsOut of a total of 200 patients included in the study, 117 patients had a low adherence (score less than 6 on MMAS) whereas 65 and 18 patients had medium (score 6 or 7) and high adherence (score of 8), respectively. The majority of patients who had low adherence to statins by MMAS were nonadherent by the pill count method yielding a concordance of 96.5%. Medium or high adherence to statins by the MMAS method had a concordance of 89.1% with the pill count method. The levels of total cholesterol, low-density lipoprotein-cholesterol, apolipoprotein B, and HMGCoA-R were negatively correlated with compliance measured by pill count and MMAS in a statistically significant way and with similar correlation coefficients. HMGCoA-R levels demonstrated a plateau phenomenon, with levels being 9-10 ng/ml when compliance with statin therapy was greater than 60% by pill count and greater than 6 on the Morisky scale.ConclusionIn conclusion, MMAS and the pill count method showed concordance in measuring adherence to statins. These methods need to be explored further for their interchangeability as surrogates for biomarker levels.

Serum levels of apolipoprotein E in colorectal cancer patients and its relationship with the diagnosis of the disease

Serum levels of apolipoprotein E in colorectal cancer patients and its relationship with the diagnosis of the disease

Comparison of apolipoprotein-A1 levels between paroxysmal atrial fibrillation patients and healthy subjects.

Introduction: Studies found that the inflammation plays a key role in the pathogenesis of paroxysmal atrial fibrillation (PAF). It is well-known that apolipoprotein-A1 (Apo-A1) demonstrates antiinflammatory and anti-oxidant properties in a healthy physiological system. In the present study, we aimed to determine whether there is any difference of Apo-A1 levels in patients with PAF and healthy subjects. Methods: In this prospective cohort study, we enrolled a total of 35 PAF patients and 34 comparable healthy participants. Apo-A1 levels were measured from each subject using an immunophelometric method. All enrolled subjects were followed-up for one year during the study period. Results: Serum high-sensitivity C-reactive protein (hs-CRP) levels were statistically higher in PAF patients compared to healthy subjects (1.54±1.99 vs. 1.06±2.01, P = 0.016, respectively). Of note, patients with PAF had lower Apo-A1 levels (1.84±0.74 vs. 2.55±0.44, P = 0.001, respectively). There was no statistical difference between the groups in terms of apolipoprotein-B levels (1.08±0.36 vs. 0.99±0.38, P = 0.339, respectively). We did not find any correlation between Apo-A1 levels and PAF attacks in the study. Conclusion: The main finding of this study was that Apo-A1 levels were significantly lower in PAF patients compared to healthy participants. Based on our results, we considered that Apo-A1 may have a key role in the pathogenesis of PAF.

Absolute Quantification of Plasma Apolipoproteins for Cardiovascular Disease Risk Prediction.

Apolipoproteins have important structural and functional roles in several lipoprotein particles. Apolipoproteins regulate lipid metabolism, adipose tissue, and energy production and serve major regulatory roles in both pre- and pro-atherosclerotic mechanisms. They are also involved in protective mechanisms against atherosclerotic plaques. Therefore, accurate quantification of apolipoproteins may serve as a crucial biomarker for cardiovascular diseases. However, most apolipoproteins cannot be detected using standard clinical immunoassays, and multiplexing is not available for some species of apolipoproteins. Herein, we describe a highly robust and quantitative method using liquid chromatography coupled to tandem mass spectrometry to quantify apolipoproteins in plasma. This methodology may add clinical value for profiling cardiovascular risk in vulnerable individuals and enable monitoring of apolipoprotein levels in plasma following intervention strategies.

Serum apolipoprotein A1: a predictor and prognostic biomarker in acute ischemic stroke

BackgroundThe apolipoprotein A1 level is recognized as a better indicator of cardiovascular disease than other cholesterol measures.ObjectivesTo assess the serum level of ApoA1 in acute stroke patients and correlate it with the degree of vessel stenosis, stroke severity, prognosis, and functional outcome.Patients and methodsWe prospectively included 60 patients with first-ever cerebrovascular ischemic stroke, and they were matched with 30 healthy individuals matched in age and sex. Patients’ neurological status was assessed via National Institute of Health and Stroke Scale (NIHSS). A venous blood sample was taken within the first 24 h of stroke onset and assayed for ApoA1 level by Human ApoA1 ELISA kit.ResultsApoA1 level could be used to discriminate between cases and controls at a level of 6.2 μg/ml, with 94.9% sensitivity and 86.6% specificity. Furthermore, there is an inverse relationship between the level of ApoA1 and the clinical outcome expressed by NIHSS score and their prognosis after 3 months. Finally, there is an inverse relationship between ApoA1 level and the degree of stenosis whether intracranial or extracranial.ConclusionApoA1 level can be used as a predictor of ischemic stroke and as a prognostic tool for those patients with ischemic stroke.