ApoA1 Levels Research Articles

Targeting ApoC3 Paradoxically Aggravates Atherosclerosis in Hamsters With Severe Refractory Hypercholesterolemia.

RationaleApoC3 plays a central role in the hydrolysis process of triglyceride (TG)-rich lipoproteins mediated by lipoprotein lipase (LPL), which levels are positively associated with the incidence of cardiovascular disease (CVD). Although targeting ApoC3 by antisense oligonucleotide (ASO), Volanesorsen markedly reduces plasma TG level and increase high-density lipoprotein cholesterol (HDL-C) in patients with hypertriglyceridemia (HTG), the cholesterol-lowering effect of ApoC3 inhibition and then the consequential outcome of atherosclerotic cardiovascular disease (ASCVD) have not been reported in patients of familial hypercholesterolemia (FH) with severe refractory hypercholesterolemia yet.ObjectiveTo investigate the precise effects of depleting ApoC3 on refractory hypercholesterolemia and atherosclerosis, we crossed ApoC3-deficient hamsters with a background of LDLR deficiency to generate a double knockout (DKO) hamster model (LDLR−/−, XApoC3−/−, DKO).Approach and ResultsOn the standard laboratory diet, DKO hamsters had reduced levels of plasma TG and total cholesterol (TC) relative to LDLR−/− hamsters. However, upon high-cholesterol/high-fat (HCHF) diet feeding for 12 weeks, ApoC3 deficiency reduced TG level only in female animals without affecting refractory cholesterol in the circulation, whereas apolipoprotein A1 (ApoA1) levels were significantly increased in DKO hamsters with both genders. Unexpectedly, loss of ApoC3 paradoxically accelerated diet-induced atherosclerotic development in female and male LDLR−/− hamsters but ameliorated fatty liver in female animals. Further analysis of blood biological parameters revealed that lacking ApoC3 resulted in abnormal platelet (PLT) indices, which could potentially contribute to atherosclerosis in LDLR−/− hamsters.ConclusionsIn this study, our novel findings provide new insight into the application of ApoC3 inhibition for severe refractory hypercholesterolemia and ASCVD.

Unbiased plasma proteomics discovery of biomarkers for improved detection of subclinical atherosclerosis.

SummaryBackgroundImaging of subclinical atherosclerosis improves cardiovascular risk prediction on top of traditional risk factors. However, cardiovascular imaging is not universally available. This work aims to identify circulating proteins that could predict subclinical atherosclerosis.MethodsHypothesis-free proteomics was used to analyze plasma from 444 subjects from PESA cohort study (222 with extensive atherosclerosis on imaging, and 222 matched controls) at two timepoints (three years apart) for discovery, and from 350 subjects from AWHS cohort study (175 subjects with extensive atherosclerosis on imaging and 175 matched controls) for external validation. A selected three-protein panel was further validated by immunoturbidimetry in the AWHS population and in 2999 subjects from ILERVAS cohort study.FindingsPIGR, IGHA2, APOA, HPT and HEP2 were associated with subclinical atherosclerosis independently from traditional risk factors at both timepoints in the discovery and validation cohorts. Multivariate analysis rendered a potential three-protein biomarker panel, including IGHA2, APOA and HPT. Immunoturbidimetry confirmed the independent associations of these three proteins with subclinical atherosclerosis in AWHS and ILERVAS. A machine-learning model with these three proteins was able to predict subclinical atherosclerosis in ILERVAS (AUC [95%CI]:0.73 [0.70–0.74], p < 1 × 10−99), and also in the subpopulation of individuals with low cardiovascular risk according to FHS 10-year score (0.71 [0.69–0.73], p < 1 × 10−69).InterpretationPlasma levels of IGHA2, APOA and HPT are associated with subclinical atherosclerosis independently of traditional risk factors and offers potential to predict this disease. The panel could improve primary prevention strategies in areas where imaging is not available.

Decreased serum apolipoprotein A1 level predicts poor prognosis of patients with de novo myelodysplastic syndromes

BackgroundMyelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that apolipoproteins A1(ApoA1) are associated with disease risk in many cancer types. However, there still lacks evidence regarding the link between ApoA1 and MDS. This study was designed to investigate the prognostic value of pretreatment ApoA1 levels in MDS patients.MethodsWe retrospectively analyzed a cohort of 228 MDS patients to explore the prognostic value of the serum ApoA1 levels at diagnosis. Patients were divided into the high ApoA1 group and the low ApoA1 group. The prognostic significance was determined by univariate and multivariate Cox hazard models.ResultsMDS patients with low ApoA1 levels had significantly shorter overall survival (OS, P < 0.0001) along with a higher frequency of TP53 mutation (P = 0.002). Based on univariate analysis, age (≥ 60 years), gender (male), lower levels of hemoglobin (< 10 g/dl), HDL (≤0.91 mmol/L), higher bone marrow blast percentage (> 5%), higher IPSS-R scores and poorer karyotype were significantly associated with decreased OS. However, low ApoA1 level did not influence leukemia-free survival (LFS, P = 0.367). Multivariate Cox proportional hazards regression analysis indicated that low ApoA1 level (≤ 1.02 g/L) was also an independent adverse prognostic factor for OS in MDS (P = 0.034).ConclusionsDecreased ApoA1 level predicts a poor prognosis of MDS patients and thus provides a novel evaluation factor for them that is independent of the IPSS-R system.

Identification of serum proteins in dogs naturally infected with Anaplasma phagocytophilum and Borrelia burgdorferi: a pilot study

Serum proteomic analysis would aid in better understanding the pathophysiology of several diseases. The aim of this study was to identify the serum proteomes of dogs with anaplasmosis and Lyme disease using a proteomic approach. Diseases were diagnosed by a commercial rapid in-clinic ELISA. Borrelia antibodies were evaluated by IFAT. Four groups were designated: symptomatic dogs with anaplasmosis (n=5), dogs with Lyme disease (n=5), dual-positive dogs (n=5), and healthy control dogs (n=5). Serum samples were collected before treatment. Two-dimensional electrophoresis of pooled samples in each group were run in triplicate. Ten out of 57 differentially expressed spots between groups were evaluated for identification by mass spectrometry. Compared to those of controls, levels of vitamin D-binding protein (VDBP), glycoprotein-9 (GP9) and kininogen-1 (KGN-1) decreased, while haptoglobin (Hp) and immunoglobulin (Ig) heavy chain levels increased in dual infection group. Serum apolipoprotein-A1 (Apo-A1) levels decreased in dogs with anaplasmosis, Lyme disease and dual infections compared to those in control dogs. Serum clusterin levels decreased in dogs with anaplasmosis but were not differentially expressed in dogs with Lyme disease or dogs with dual infections compared to those in control dogs. Calpain-3 decreased in dogs with anaplasmosis and Lyme disease. This study showed that many protein levels might be changed in dogs with naturally acquired anaplasmosis and Lyme disease. Understanding the role of these proteins in different biological processes can provide information of interest for diagnostic and therapeutic approaches for these clinical conditions.

Daeshiho-tang Attenuates Atherosclerosis by Regulating Cholesterol Metabolism and Inducing M2 Macrophage Polarization.

Dyslipidemia, the commonest cause of cardiovascular disease, leads to lipid deposits on the arterial wall, thereby aggravating atherosclerosis. DSHT (Daeshiho-tang) has long been used as an anti-dyslipidemia agent in oriental medicine. However, the anti-atherosclerotic effects of DSHT have not been fully investigated. Therefore, this study was designed to evaluate whether DSHT could exert beneficial anti-atherosclerotic effects. We fed apolipoprotein E-deficient (ApoE-/-) mice on a high-fat diet and treated them with atorvastatin (AT) or DSHT, or the combination of DSHT and AT for 12 weeks. To determine the role of DSHT, atherosclerotic lesions in the aorta, aortic root, and aortic arch; lipids and apolipoprotein levels in serum; and macrophage polarization markers in aorta tissues were examined. We show here that the DSHT decreased the atherosclerotic plaque ratio in the aortic arch, aorta, and aortic root. DSHT also regulated lipid levels by decreasing the ApoB level and increasing the ApoA1 level. Moreover, DSHT effectively regulated cholesterol metabolism by increasing the levels of PPARγ, ABCA1 and ABCG1, and the LDL receptor genes. We further found that DSHT promoted polarization to the M2 phenotype by increasing the levels of M2 macrophage (ARG1, CD163, and PPARγ) markers. Our data suggested that DSHT enhances the anti-atherosclerotic effect by regulating cholesterol metabolism through the activation of the PPARγ signaling pathway and by promoting anti-inflammatory M2 macrophage polarization.

Low-density lipoprotein receptor and apolipoprotein A 5, myocardial infarction biomarkers in plasma-derived exosomes

ObjectivesMyocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. Previously, rare mutations in low-density lipoprotein receptor (LDLR) genes and apolipoprotein A V (APOA5) have been shown to contribute to MI risk in individual families. Exosomes provide a potential source of biomarkers for MI. This study is to determine the role of LDLR and APOA5 as biomarkers for early diagnosis of MI. MethodsIn this study, we detected the levels of LDLR, APOA5, and cardiac troponin T in plasma-derived exosomes in MI patients and age-matched healthy people by enzyme linked immunosorbent assay and observed the morphology and number of exosomes using transmission electron microscope and nanoparticle tracking analysis. Oxygen-glucose deprivation (OGD) method was used to induce MI in H9C2 cardiomyocytes to explore the effect of exosomes. ResultsWe found that the levels of LDLR and APOA5 in plasma-derived exosomes in MI patients were significantly decreased. Furthermore, exosomes of MI patients were significantly larger in size and the concentration of exosomes was higher than that of age-matched non-MI people. In vitro experiments showed that OGD treatment induced apoptosis of myocardial cells and decreased the expression of LDLR and APOA5, while addition of exosomes isolated from healthy people rescued these phenotypes. ConclusionExosomal APOA5 and LDLR are intimately associated with MI, and thereby have the potential to function as diagnostic markers of MI.

Association of Serum Apolipoprotein A5 Concentration with Nonalcoholic Fatty Liver Disease in Ningbo, China.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease characterized by the excessive accumulation of hepatocyte fat and steatosis in the absence of alcohol or any other clear contributing factors to liver injury. NAFLD has been confirmed to be closely associated with obesity, insulin resistance, and dyslipidemia. Genetic polymorphism studies have shown the relations between the apolipoprotein A5 gene (APOA5) and NAFLD. However, the association between the serum ApoA5 level and NAFLD remains unclear. Between September 2018 and August 2019, adults who attended the hospital-based health checkup center were enrolled in this study. Anthropometric examination, laboratory investigations on fasting blood, and abdominal ultrasonography were performed. The serum ApoA5 level was determined by enzyme-linked immunosorbent assay. A total of 517 eligible participants (317 females and 200 males) were involved in this study, with a mean age of 54.7 ± 16.7 years. The mean ApoA5 concentration was 28.8 ± 4.7 μg/ml, among which the males had higher concentration levels than females (29.3 ± 4.5 vs. 28.5 ± 4.7 μg/mL, P=0.04). Serum ApoA5 level was not significantly correlated with NAFLD or metabolic profiles. However, the prevalence rate of hypertriglyceridemia (triglyceride ≥ 1.7 mmol/L) showed a significant inverted “U”-shaped trend in individuals with the serum ApoA5 level of quartile one to quartile four after adjusting the confounding factors. Moreover, individuals with higher serum ApoA5 levels were also more likely to suffer from hyperglycemia. The ApoA5 levels and the prevalence of hypertriglyceridemia are in an inverted “U-shaped” correlation, but there is no significant difference between ApoA5 levels, NAFLD, and metabolic syndrome.

Association Between Blood Lipid Levels and Lower Extremity Deep Venous Thrombosis: A Population-Based Cohort Study.

ObjectsTo investigate the potential clinical significance between blood lipid levels and lower extremity deep venous thrombosis (LEDVT). Methods: This cohort study included 500 participants, contains 246 patients with LEDVT and 254 patients without LEDVT. The characteristics including age, sex, body mass index (BMI), disease course, ill position, smoking history, history of current illness, drug administration were collected. And blood lipid levels and other clinical parameters including triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), activated partial thromboplastin time (APTT), thromboplastin time (TT), prothrombin time (PT), and fibrinogen (FIB), neutrophils (NEUT), platelet (PLT), lymphocyte count (LY) were observed. Univariate and multivariate logistic regression analyses were applied. In the present study we particularly focused on the potential associations between blood lipid levels and LEDVT. Results: The risk of LEDVT in participants with HDL-C levels of 0.965 to 1.14 mmol/L, 1.14 to 1.36 mmol/L, and >1.36 mmol/L were 0.366, 0.183, 0.203 times than in controls (<0.965 mmol/L), respectively. Compared to individuals with ApoA1 <1.06 mmol/L, individuals with ApoA1 levels of 1.06 to 1.22 mmol/L, 1.22 to 1.38 mmol/L, and >1.38 mmol/L were related to a decreased risk of LEDVT. The risk of LEDVT in patients with TG levels of 0.985 to 1.37 mmol/L, 1.37 to 1.91 mmol/L, and >1.91 mmol/L were 2.243, 2.224, and 2.540 times higher than that of those with TG <0.985 mmol/L, respectively. The risk of LEDVT in subjects with 4.57< TC <5.17 mmol/L was 0.471-fold than that of those with TC <3.97 mmol/L. Conclusion: The present study indicates that higher levesl of HDL-C and ApoA1 could be associated with a decreased risk of LEDVT, while higher TG levels might be associated with an increased risk of LEDVT. In addition, within the normal range, high TC levels were associated with decreased risk of LEDVT. These findings may help clinicals to identify early and treat those patients with a high-risk of LEDVT at proper time, which could improve patients’ life quality.

Exercise Alleviates the Apolipoprotein A5-Toll-Like Receptor 4 Axis Impairment in Mice With High-Fat Diet-Induced Non-alcoholic Steatohepatitis.

Background: Apolipoprotein A5 (ApoA5), an important modulator of plasma and hepatic triglyceride metabolism, has been found to be downregulated by metformin to improve non-alcoholic fatty liver disease. Meanwhile, exercise has been recommended as a therapeutic strategy for non-alcoholic steatohepatitis (NASH). However, no study has yet determined whether exercise affects hepatic ApoA5 expression or the inhibition of ApoA5 to toll-like receptor 4 (TLR4). We herein examined the effects of exercise on hepatic ApoA5 expression and the relevance of ApoA5 and TLR4-mediated pathway in mice with high-fat diet (HFD)-induced NASH.Methods: Male C57BL/6J mice were built NASH model with high-fat diet for 12 weeks, and following mice were subjected to exercise for 12 weeks on a treadmill. Microscopy and enzyme-linked immunosorbent assay were used to measure histological analysis of liver and hepatic lipids, respectively. Quantitative real-time PCR and western blot were used to determined mRNA and protein levels of ApoA5 and TLR4-mediated nuclear factor kappa B (NF-κB) pathway components, respectively. ApoA5 overexpression plasmids transfected into mice to investigate the relevance of ApoA5 and TLR4.Results: 12 weeks of exercise remarkably alleviated HFD-induced hepatic lipid accumulation, inflammation, and fibrosis, as well as reduced serum lipopolysaccharide (LPS), hepatic TLR4, myeloid differentiation factor 88 (MyD88), and NF-κBp65 expression. Importantly, exercise did not reduce ApoA5 expression but instead enhanced its ability to suppress TLR4-mediated NF-κB pathway components by decreasing circulating LPS in our experiments involving transfection of ApoA5 overexpression plasmids and LPS interventions.Conclusion: The results demonstrated that exercise improved HFD-induced NASH by triggering the inhibitory effects of ApoA5 on the TLR4-mediated NF-κB pathway.

Bariatric Surgery Leads to a Reduction in Antibodies to Apolipoprotein A-1: a Prospective Cohort Study

PurposeAutoantibodies against apolipoprotein A-1 have been associated with cardiovascular disease, poorer CV outcomes and all-cause mortality in obese individuals. The impact of bariatric surgery (BS) on the presence of circulating anti-apoA-1 IgG antibodies is unknown. This study aimed to determine the effect of bariatric surgery on auto-antibodies titres against Apolipoprotein A-1 (anti-apoA-1 IgG), looking for changes associated with lipid parameters, insulin resistance, inflammatory profile and percentage of excess body mass index loss (%EBMIL).Materials and MethodsWe assessed 55 patients (40 women) before, 6 and 12 months post-operatively. Baseline and post-operative clinical history and measurements of body mass index (BMI), serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), apoA-1, highly sensitive C-reactive protein (hsCRP), fasting glucose (FG), glycated haemoglobin (HbA1c) and HOMA-IR were taken at each point. Human anti-apoA-1 IgG were measured by ELISA.ResultsThe mean age of participants was 50 years. BS significantly improved BMI, %EBMIL triglycerides, HDL-C, apoA-1, hsCRP, HBA1c, FG and HOMA-IR. Baseline anti-apoA-1 IgG seropositivity was 25% and was associated with lower apoA-1 and higher hsCRP levels. One year after BS, anti-apoA-1 IgG seropositivity decreased to 15% (p = 0.007) and median anti-apoA-1 IgG values decreased from 0.70 (0.56–0.84) to 0.47 (0.37–0.61) AU (p < 0.001). Post-operative anti-apoA-1 IgG levels were significantly associated with a decreased post-surgical %EBMIL at 1 year.ConclusionBariatric surgery results in significant reduction in anti-apoA-1 IgG levels, which may adversely influence weight loss. The exact mechanisms underpinning these results are elusive and require further study before defining any clinical recommendations.Graphical abstract

Serum apolipoprotein A1 rather than apolipoprotein B is associated with hypertension prevalence in Chinese people with coronary artery disease.

Studies on the association of apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) with hypertension (HTN) prevalence in patients with coronary artery disease (CAD) are limited. This cross-sectional study aimed to investigate this association in Chinese people in Wuhan, China. Serum ApoA1 and ApoB levels were measured by immunoturbidimetry assay. Logistic regression analysis was used to estimate the associations of ApoA1 and ApoB level and ApoB/A1 ratio with HTN prevalence. We included 5192 individuals (3060 men, mean age 61 years; 4412 HTN cases) in this study. After adjusting for covariates, serum ApoA1 but not ApoB level or ApoB/A1 ratio was inversely associated with HTN prevalence. HTN prevalence was reduced with the fifth versus first quintile of ApoA1 level [odds ratio = 0.78 (95% confidence interval 0.62-0.98)]. In stratified analyses based on sex, the probability of HTN with the fifth versus first ApoA1 level was 0.71 (0.53-0.96) for men. The probability of HTN with the fifth versus first quintile of ApoB/A1 ratio was 1.54 (1.11-2.13) after adjustment. With quintiles 2-5 versus of ApoB level, the probability of HTN did not differ in both men and women. On path analyses, the association of ApoA1 level and ApoB/A1 ratio with HTN was mediated by BMI (β coefficients: -0.179 to 0.133). In general, high serum ApoA1 level may be associated with a reduced probability of HTN prevalence in patients with CAD in China, and this association may be mediated by BMI.

The Variants at APOA1 and APOA4 Contribute to the Susceptibility of Schizophrenia With Inhibiting mRNA Expression in Peripheral Blood Leukocytes.

Objective: Abnormal lipid metabolism has a close link to the pathophysiology of schizophrenia (SZ). This study mainly aimed to evaluate the association of variants at apolipoprotein A1 (APOA1) and APOA4 with SZ in a Chinese Han population. Methods: The rs5072 of APOA1 and rs1268354 of APOA4 were examined in a case–control study involving 2,680 patients with SZ from the hospital and 2,223 healthy controls screened by physical examination from the community population. The association was estimated with the odds ratio (OR) and 95% confidence intervals (95% CIs) by logistic regression. The APOA1 and APOA4 messenger RNA (mRNA) in peripheral blood leukocytes were measured by real-time PCR and compared between SZ cases and controls. Serum apoA1 levels were detected by turbidimetric inhibition immunoassay and high-density lipoprotein cholesterol (HDL-C) levels were detected by the homogeneous method. Results: Both of the rs5072 of APOA1 and rs1268354 of APOA4 had statistically significant associations with SZ. After adjustment for age and sex, ORs (95% CIs) of the additive model of rs5072 and rs1268354 were 0.82 (0.75–0.90) and 1.120 (1.03–1.23), and p-values were 3.22 × 10−5 and 0.011, respectively. The association of rs5072 with SZ still presented statistical significance even after Bonferroni correction (p-value×6). SZ patients during the episode presented lower levels of apoA1, HDL-C, mRNA of APOA1 common variants and transcript variant 4, and APOA4 mRNA than controls (p < 0.01) while SZ patients in remission showed a significantly decreased APOA1 transcript variant 3 expression level and increased APOA4 mRNA expression level (p < 0.01). mRNA expression levels of APOA1 transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (p trend = 0.017). After the SZ patients received an average of 27.50 ± 9.90 days of antipsychotic treatment, the median (interquartile) of serum apoA1 in the SZ episode significantly increased from 1.03 (1.00.1.20) g/L to 1.08 (1.00.1.22) g/L with the p-value of 0.044. Conclusion: Our findings suggest that the genetic variations of APOA1 rs5072 and APOA4 rs1268354 contribute to the susceptibility of SZ, and the expression levels of APOA1 and APOA4 mRNA of peripheral blood leukocytes decreased in SZ patients during the episode while APOA4 increased after antipsychotic treatment.

Association between clinical symptoms and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia

BackgroundThe apolipoprotein E (ApoE) gene polymorphisms are correlated with blood lipid levels and several neuropsychiatric symptoms. Therefore, this study aimed to examine whether the ApoE rs429358 affected the development and clinical symptoms of schizophrenia and to explore the relationship between apolipoproteins levels and clinical symptoms.MethodsThe ApoE rs429358 was genotyped using a case–control design. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate the psychopathology of all patients.ResultsA total of 637 patients with schizophrenia and 467 healthy controls were recruited. We found no significant differences in the genotype and allele distribution between the patient and control groups. A significant correlation between PANSS negative symptoms and ApoA1 levels (p = 0.048) or ApoB levels (p = 0.001) was found in patients with schizophrenia, which was also confirmed by linear regression analyses (p = 0.048 vs. p = 0.001). Interestingly, only in the T homozygote group, ApoA1 and ApoB levels were predictors of the PANSS negative symptom score (p = 0.008 vs. p = 0.012), while in the C allele carrier group, no correlation was observed.ConclusionsThis study found that the levels of ApoA1 and ApoB were negatively associated with negative symptoms of patients with schizophrenia. Furthermore, the association between ApoA1 or ApoB levels and psychopathology of schizophrenia was regulated by ApoE rs429358.

Prevalence, clinical correlates and risk factors associated with Tardive Dyskinesia in Chinese patients with schizophrenia.

Tardive Dyskinesia (TD) is a serious, nonrhythmic and iatrogenic movement disorder, and is a common comorbidity in patients with schizophrenia (SZ). The main goal of this study was to investigate the prevalence, clinical correlates, and risk factors of TD in Chinese patients with chronic SZ, which has not been fully studied. This study adopted a cross-sectional design. A total of 901 Chinese inpatients with SZ were recruited between 2008 and 2011. We used the Abnormal Involuntary Movement Scale (AIMS) to measure the severity of TD, and the Positive and Negative Syndrome Scale (PANSS) was used to measure the psychopathological symptoms of SZ. Blood samples were also collected for routine blood tests, including the levels of triglyceride (TG), cholesterol (CHO), HDL-cholesterol (HDL-CHO), LDL-cholesterol (LDL-CHO), Apolipoprotein A1 (ApoA1), and Apolipoprotein B (ApoB). Overall, 36% of patients with SZ had TD. Compared with the non-TD patients, the TD patients were more likely to be men, had older age, lower education level, higher smoking rate, higher hospitalization frequency, and longer duration of illness (DOI). Further, compared with the non-TD patients, the TD patients had higher PANSS total, PANSS negative subscale, and cognitive subscale scores, but had lower depressive subscale scores and lower mean levels of metabolic biomarkers, including TG, CHO, HDL-CHO, LDL-CHO, ApoA1 and ApoB. Moreover, binary regression analysis showed that antipsychotic type, BMI, gender, age, HDL-CHO, and ApoB were associated with TD. Our findings indicate that TD is a common movement disorder in patients with chronic SZ, with certain demographic and clinical variables being risk factors for the development of TD.

A systematic review and meta-analysis on the impact of oral vitamin E supplementation on apolipoproteins A1 and B100

Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. Apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), and ApoB/ApoA1 ratio are considered as predictors of CVD alongside with lipid profile. Evidence suggest that nutrients with antioxidant properties, especially vitamin E, are essential for a healthy cardiovascular system. The aim of present meta-analysis was to determine the effect alpha-tocopherol on ApoA1 and ApoB levels. PubMed-Medline and SCOPUS databases and Google Scholar were searched up to July 2021. Random-effects model was employed to perform meta-analysis. In order to find heterogeneity sources, subgroup analysis was performed. Trim and fill analysis was performed in case of presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. Seven eligible studies, involving 1284 individuals were included. Mean age of participants ranged between 25.4 and 59 years. There was no significant effect of vitamin E supplementation on Apo A1 (SMD=0.22 IU/d; 95% CI:-0.38, 0.28; P=0.481) and Apo B levels (SMD=-0.62 IU/d; 95% CI:-1.94, 0.70; P=0.360). No remarkable effect of vitamin E supplementation was observed on ApoA1 and ApoB levels in adults. Additional studies investigating the influence of vitamin E on apolipoproteins as primary outcome with larger sample size are suggested.

Plasma Aβ40, Aβ42 and Aβ‐clearance proteins as blood biomarkers for Alzheimer's disease, subjective cognitive decline, and MCI

AbstractBackgroundFor early intervention and prevention of dementia, diagnostic biomarkers for MCI and preclinical Alzheimer's disease (AD) are important. amyloid β (Aβ) and tau are known as biomarkers for AD, and the CSF Aβ40 / Aβ42 ratio is clinically useful for diagnosis of AD. We have reported that three proteins in serum related to Aβ clearance: ApoA1, complement protein C3 and transthyretin (TTR) are useful as blood biomarkers for MCI (Triple marker). Plasma Aβ has been shown to correlate with amyloid PET, however, its clinical utility in MCI and AD diagnosis is unclear. Therefore, we investigated usefulness plasma Aβ in addition to the triple marker as blood test for MCI and AD. Here we analyzed plasma levels of Aβ40, Aβ42 and Triple marker in MCI and AD as diagnostic markers.MethodA total of 909 cases consisting of 354 non‐demented control (NDC), and 76 subjective cognitive decline (SCD), 312 MCI, and 167 AD diagnosed according to ADNI neuropsychological criteria were selected in the multicenter clinical study. The positron emission tomography (PET) using with [18F] Florbetapir was performed 24 APOE4‐carring SCD and MCI subjects. Plasma Aβ40, Aβ42 were measured by ELISA (EUROIMMUN, Lübeck). Plasma levels of ApoA1, TTR, complement C3 was measured as described previously (Liu et al., Alzheimer Dement (Amst) 2019).ResultPlasma ApoA1 and complement C3 levels were decreased in progression of the disease. Plasma Aβ40 / 42 ratio showed ROC AUC = 0.82 and 0.67 in AD vs. NDC and MCI vs. NDC, respectively. Combination of plasma levels of Aβ40 / 42 ratio and Triple marker (ApoA1, TTR, C3) showed AUC = 0.85 (80% sensitivity and 85% specificity) in AD vs. NDC and AUC = 0.76 (76% sensitivity and 70% specificity) in MCI vs. NDC. Aβ40 / 42 ratio and TTR were significantly decreased in amyloid‐positive subjects (SUVR≥1.10) compared to amyloid‐negative subjects (SUVR&lt;1.10).ConclusionCombination of plasma Aβ40 / Aβ42 ratio and Triple marker is a useful blood test for not only AD but also the early stages of cognitive decline.

Disorders of lipid metabolism and lipid transport system in women with unstable angina in the dependence on smoking: pathogenetic connections and development risks

The aim of the study. To study the effect of smoking on lipid metabolism, lipid transport system and systemic inflammation, to find out their correlations and the risks of unstable angina in women, depending on the habit of smoking.Material and methods. 225 women were examined: 150 women - patients with unstable angina and 75 healthy women. The level of total cholesterol, low and high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 (ApoA1) and B (ApoB), C-reactive protein, fibrinogen were determined in all subjects. Multifactor correlation-regression analysis was performed using Fisher's test. Statistical processing of the results was performed using the applications "Microsoft Office Excel 2016" and "Statistics ver. 10.Results. The relative risk of developing unstable angina in patients with a smoking habit is most often associated with atherogenic dyslipidemia (total cholesterol &gt; 4 mmol, OR = 12.02, SI = 8.12-16.32; low-density lipoprotein cholesterol &gt; 1.8 mmol / l, OR = 9,32, SI = 6,13-12,56, high-density lipoprotein cholesterol &lt;1,2 mmol / l, OR = 3,91, SI = 2,12-5,45, the ratio of apolipoproteins ApoV / ApoA1&gt; 0.85, OR = 2.69, SI = 1.15-4.21) and the highest activity of systemic inflammation (C-reactive protein &gt;3 mg / l, OR = 3.62, SI = 2.15- 4.56). The risk of developing unstable angina associated with these indicators is 1.5-2 times higher in women with a smoking habit than in women who have never smoked. Significant direct correlations of high and medium strength between the severity of systemic inflammation, disorders of the lipid transport system (increase in the ratio of ApoB / ApoA1 and decrease in the level of ApoA1), in patients with unstable angina in women smokers.Conclusions. Smoking is one of the most aggressive factors of unstable angina in women, which contributes to the emergence and progression of other important risk factors and leads to disorders of lipid metabolism, lipid transport system, systemic inflammation and increased chances of unstable angina.

Associations of Serum Calcium, Magnesium Levels, and Their Ratio with Apolipoproteins in Chinese Adults with Coronary Artery Disease: a Cross-Sectional Study.

Former evidence regarding the associations of serum calcium (Ca) and magnesium (Mg) levels with apolipoproteins (Apos) in Chinese adults with coronary artery disease (CAD) were scarce. A total of 6781 patients with CAD were included in this cross-sectional study; mean age was 61.0years. The associations of serum Ca, Mg, and Ca/Mg ratio with Apos (e.g., ApoA1, ApoB, and ApoB/A1 ratio) were determined using multivariate analysis of covariance. Serum Ca, Mg, and Ca/Mg ratio tended to have positive associations with ApoA1, while negative associations of serum Ca, Mg, and Ca/Mg ratio with ApoB and ApoB/A1 ratio were detected. In multivariate analysis, serum Ca, Mg, and Ca/Mg ratio were positively associated with ApoA1 levels (Q [quintile] 5 vs. Q1: 1.245 vs. 1.151g/L for Ca, 1.207 vs. 1.188g/L for Mg, 1.202 vs. 1.171g/L for Ca/Mg ratio). In contrast, negative associations of serum Mg and Ca/Mg ratio with ApoB and ApoB/A1 ratio were shown. The corresponding ApoB and ApoB/A1 ratio values were 0.856 (vs. 0.887g/L) and 0.728 (vs. 0.771) for Mg, and 0.814 (vs. 0.854g/L) and 0.695 (vs. 0.751) for Ca/Mg ratio in Q5 compared with Q1. Serum Ca was inversely associated with ApoB and ApoB/A1 ratio (Q5 vs. Q4: 0.804 vs. 0.847g/L for ApoB; Q5 vs. Q1: 0.662 vs. 0.732 for ApoB/A1 ratio). Path analysis showed that mediating effects of BMI on the "Ca or Mg-Apos" associations were not found. In summary, serum Ca and Mg tended to have positive associations with ApoA1 levels in patients with CAD, but had inverse associations with ApoB levels and ApoB/A1 ratio. Serum Ca/Mg ratio may be a more precise marker than serum Mg or serum Ca measures alone in assessing Apos measures of CAD risk.

Association between Genetic Polymorphisms of MIR3142HG and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China

Background: Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of MIR3142HG on steroid-induced ONFH. Methods: Agena MassARRAY was used to genotype MIR3142HG gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the MIR3142HG polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. Results: The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (p = 0.012) and ApoA1 (p = 0.010) levels, and rs17057846 (p = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in MIR3142HG with significant chain imbalance. In addition, haplotype “GGG” of MIR3142HG was found out and is harmful for steroid-induced ONFH. Conclusion: Our results first confirm that the genetic polymorphism of MIR3142HG is associated with steroid-induced ONFH susceptibility in Chinese Han population.

Serum Vitamin D Levels and Risk Factors for Cardiovascular Complication in Diabetes

BACKGROUND: Diabetes is a significant contributor to dyslipidemia, which can contribute in cardiovascular complications. Vitamin D is crucial in preventing chronic metabolic diseases such as diabetes and heart disease (cardiovascular disease [CVD]). AIM: The objective of this study was to determine the relationship between Vitamin D levels and cardiovascular risk in type 2 diabetes mellitus. MATERIALS AND METHODS: This study is cross-sectional in nature. The study sampled 89 diabetic patients who met the study’s inclusion and exclusion criteria. After a 10 h fast, a venous blood test is performed to determine Vitamin D levels, apolipoprotein-A levels, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. The data are analyzed using SPSS. The Pearson correlation test (p &gt; 0.05) was used to determine the connection. RESULT: Vitamin D levels were found to correlate with Apo-A1, TC, HDL-C, and triglyceride levels (p = 0.05), but not with LDL-C levels (p &gt; 0.05). CONCLUSION: Vitamin D supplementation may assist DMT2 patients minimize their chance of developing CVD problems.