Apolipoprotein A1 Research Articles

Attenuation of high-fat diet-induced weight gain by apolipoprotein A4.

Apolipoprotein A4 (APOA4) is synthesized by the small intestine in response to dietary lipids. Chronic exposure to a high-fat diet (HFD) desensitizes lipid-induced APOA4 production and attenuates brown adipose tissue (BAT) thermogenesis. We hypothesized that exogenous APOA4 could increase BAT thermogenesis and energy expenditure in HFD-fed mice, resulting in decreased obesity and improved glucose tolerance. BAT and inguinal white adipose tissue (IWAT) thermogenesis, body composition, energy intake and expenditure, and locomotor activity were measured using an infrared camera, immunoblots, quantitative magnetic resonance imaging, and a comprehensive lab animal monitoring system. An intraperitoneal glucose tolerance test and hepatic lipid accumulation and steatosis were assayed. Mice receiving continuous infusion of APOA4 for the last 4 weeks of 10 weeks of HFD feeding gained no additional body weight and had reduced fat mass but enhanced BAT and IWAT thermogenesis and energy expenditure, despite unaltered food intake and locomotor activity. Additionally, APOA4 infusion elevated fatty acid β oxidation; decreased lipogenesis, lipid accumulation, and steatosis in liver; and improved glucose tolerance. Maintenance of plasma APOA4 via exogenous APOA4 protein parallels elevation of BAT and IWAT thermogenesis, hepatic fatty acid β oxidation, and overall energy expenditure, with subsequent prevention of additional weight gain in HFD-fed obese mice.

Abstract 4119635: The Effect of Exercise Training on Apolipoproteins: A Trial Sequence Meta-Analysis.

Background: The role of lipoprotein sub-units in the development of CVD not as well understood as for the standard lipid profile. We conducted a systematic review and meta-analysis of the effect of Exercise training (ExTr) effect on common lipid sub-units. Methods: We conducted a systematic search for randomized, controlled trials of ExTr versus sedentary controls that reported lipid sub-units Apo AI, Apo AII, Apo B, HDL-2, HDL-3 and Lp(a) up until January 31, 2024. Results: We included 24 included studies with 27 intervention groups, with a total of 1,429 participants, 775 ExTr and 654 control. We found significant favourable anti-atherogenic changes in Apo A1; MD 5.96 mg/dL 95% CI (3.63, 8.30); Apo B; MD -0.11 mg/dL (-0.19, -0.04); HDL-2; MD 1.28 mg/dL 95% CI (0.28, 2.28). Our TSA analysis showed that futility was achieved for Apo A1, but not for Apo B and HDL-2. The minimal clinically important differences (MCID) for Apo A1, Apo B and HDL-2 were 0.76 mg/dL, 0.02 mg/dL and 0.26 mg/DL respectively, meaning ExTr is capable of adequately achieving clinical significance for these 3 outcomes. Analyses of Apo A2, Lp(a)and HDL-3 were not significant and these TSA analyses failed to show futility. Conclusion: ExTr produces significant improvements in ApoA1, Apo B and HDL-2, with the MCID achieved and evidence of futility reached for all three of these outcomes. The effect of ExTr on Apo A2, Lp(a)and HDL-3 is unclear as futility has not been reached. ExTr changes observed in Apo AI are similar in size to those from statin trials that were associated with an 11% reduction in CV events.

Abstract 4138633: Infusion of human apolipoprotein A-I (CSL112) promotes several aspects of reverse cholesterol transport

Background: High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent apolipoprotein A-I (apoA-I), to increase reverse cholesterol transport. Objective: To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI). Methods: A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in ex vivo cell-based assays. Results: CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC strongly correlated with cholesterol uptake by hepatic cells (r=0.95 p<0.001). Conclusion: CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway.

Abstract 4136758: Apabetalone: evaluating cardiovascular and safety outcomes in meta-analysis

Background: Epigenetic mechanisms play a pivotal role in the transcriptional programs associated with cardiovascular disease (CVD). Apabetalone, an orally available inhibitor of BET proteins that serve as key epigenetic readers, and modulating gene expression - holds promise as a therapeutic intervention in CVD management. Understanding its efficacy and tolerability is crucial for delineating its potential impact on disease progression and patient outcomes. Purpose: This systematic review and meta-analysis aimed to assess the impact of apabetalone in patients with cardiovascular disease. Methods: The meta-analysis was registered with PROSPERO (CRD42023423298). Databases searched included Cochrane CENTRAL, PubMed, Ovid Medline, and Web of Science. Three unique RCTs with total of 2897 patients were included, with trial durations ranging from 12 to 124 weeks. Primary outcomes assessed were all-cause mortality and non-fatal myocardial infarction (MI). Data analysis was performed using the inverse variance common effect model. Subgroup analyses were conducted based on the presence of atherosclerotic cardiovascular disease (ASCVD) or its increased risk. Results: Among the primary outcomes, no significant effects of apabetalone were observed on all-cause mortality (RR 0.88, 95% CI 0.63 to 1.23) or non-fatal MI (RR 0.83, 95% CI 0.62 to 1.11). Apabetalone demonstrated favorable effects on increasing Apo A1 (SMD 0.20, 95% CI 0.04 to 0.35) and HDL (SMD 0.29, 95% CI 0.09 to 0.49). However, no significant effects were observed for changes in Apo B, LDL, non-HDL, total cholesterol. Subgroup analysis did not reveal any significant differences in outcomes. Significant effects were noted in secondary outcomes. Apabetalone showed a significant increase in adverse events (AEs) leading to withdrawal (RR 1.61, 95% CI 1.21 to 2.15) and ALT and AST increases greater than three times the normal value (RR 4.50, 95% CI 2.73 to 7.41). Conclusion: Our meta-analysis highlights the significant impact of apabetalone on certain lipid parameters and adverse events. However, it did not demonstrate significant effects on all-cause mortality or non-fatal MI. Further well-designed and reported RCTs were warranted to elucidate the clinical implications of apabetalone in selected group of patients that might benefit the most from apabetalone that may also improve cardiovascular disease management.

Effect of dyslipidemia on HBsAg clearance in nucleos(t)ide analogues-experienced chronic hepatitis B patients treated with peginterferon alfa.

While previous reports have shown that hepatitis B virus (HBV) infection affects lipid metabolism and vice versa, the impact of dyslipidemia on the functional cure of HBV infection following peginterferon alfa (PegIFNα) therapy remains unknown. Hence, this study aimed to investigate the effect of dyslipidemia on hepatitis B surface antigen (HBsAg) clearance and develop a nomogram model for predicting patients for whom PegIFNα therapy is indicated. A total of 160 nucleos(t)ide analogues (NAs)- experienced chronic hepatitis B (CHB) patients treated with PegIFNα (180µg/week) were enrolled in this study. The relationship between serum lipid and HBsAg clearance was analysed. Univariate and multivariate COX analyses were used to construct and plot the nomogram model. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. After 48 weeks of PegIFNα therapy, a total of 33 patients in the cohort achieved HBsAg clearance. Univariate and multivariate COX analyses indicated that dyslipidemia was significantly associated with HBsAg clearance and was an independent predictor of HBsAg clearance (HR = 0.243, P = 0.001). Kaplan-Meier survival analyses show that cumulative HBsAg clearance was significantly higher in the normolipidemic group than in the dyslipidemia group (log-rank test, P = 0.007). During the treatment, triglyceride showed an increasing trend, while the levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein A1 and apolipoprotein B decreased. Dyslipidemia and other indicators independently associated with HBsAg clearance were used to construct the nomogram model. The AUC of the model at 36-week and 48-week were 0.879 and 0.856, and the model demonstrated good discrimination and calibration. Dyslipidemia can affect the antiviral efficacy of PegIFNα in NAs-experienced CHB patients. Our findings suggest that the nomogram model constructed using serum lipid has good predictive power and may help physicians to identify the superior patients for PegIFNα therapy.

Risk factors associated with the false positive of cardiopulmonary exercise test in the diagnosis of coronary heart disease.

Cardiopulmonary exercise test (CPET) is a common method for preliminary evaluating coronary heart disease (CHD), but it may experience false positive. The present study aimed to reveal the potential factors relating to the false positive of CPET, including blood glucose and lipids. This observational cohort study included 103 subjects with false positive of CPET and 65 subjects with true positive of CPET. The baseline characteristics, blood glucose, and blood lipids between the true and false positive groups were compared. After adjusting for the age and sex, logistic regression analysis was performed to reveal the potential risk factors of false positive. Receiver operating characteristic curve analysis was performed to evaluate the potential of related factors in distinguishing between true and false positive results. Males, smokers, and patients with diabetes were less likely to suffer from false positive of CPET. Compared with the true positive group, the false positive group exhibited significantly higher levels of high-density lipoprotein (HDL) and apolipoprotein A1 (Apo-A1), and lower levels of fasting blood glucose (FBG) and glycosylated hemoglobin (GHb). After adjustment, FBG and GHb were protective factors of the true positive of CPET, and they both had moderate ability to distinguish false positive from true positive in females. However, their combination did not improve the discriminative effect more obviously than FBG alone. Sex, smoking, diabetes, and blood glucose were associated with the false positive of CPET. FBG was valuable in predicting the risk of false positive of CPET in females with suspected CHD. The present study is registered in Chinese Clinical Trial Register (ChiCTR2400089239).

Apolipoprotein A1-encoding recombinant adenovirus remodels cholesterol metabolism in tumors and the tumor microenvironment to inhibit hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor requiring effective treatments. Oncolytic viruses induce anti-tumor responses but have limited efficacy. Apolipoprotein A1 (ApoA1) inhibits inflammation, modulates immunity, and promotes anti-oxidation. This study aims to construct an oncolytic adenovirus (Ad5)-ApoA1 for superior anti-tumor effects.We analyzed ApoA1 expression in tumors and its prognostic significance using public databases. Subsequently, we engineered a recombinant oncolytic adenovirus Ad5-ApoA1 and assessed its replication and oncolytic efficacy in vitro and in nude mice. The impact of Ad5-ApoA1 on the tumor microenvironment of HCC was evaluated through flow cytometry, transcriptome sequencing, single-cell sequencing, and other methodologies. Additionally, mechanisms of immune microenvironment modulation by Ad5-ApoA1 were explored. ApoA1 expression was down-regulated with HCC progression and significantly positively correlated with the prognosis of HCC patients. Ad5-ApoA1 exhibited robust oncolytic activity but showed no therapeutic effect on nude mice. However, it significantly inhibited HCC growth and prolonged the survival period of both healthy-immune and humanized immune-reconstituted NCG mice. Furthermore, Ad5-ApoA1 significantly promoted the expression of IFN-γ and GzmB in CD8+ T cells while inhibiting the expression of PD-1 and LAG-3. Notably, the cholesterol content in the CD8+ T cells studied was significantly correlated with the expression of PD-1 and LAG-3, with ApoA1 promoting cholesterol efflux and reducing cholesterol levels. Ad5-ApoA1 activates CD8+ T cells by promoting large-scale viral replication. High levels of ApoA1 protein expression promote cholesterol efflux, inhibit CD8+ T cell depletion, and reduce inflammatory factors, ultimately leading to superior therapeutic effects on hepatocellular carcinoma.

Quantitative analysis of dried serum FTIR spectra based on correlation Analysis-Interval random Frog-Partial least squares

Serum biochemical markers are widely used in clinical practice but often require expensive, specific reagents, complex instruments, and prolonged result waiting times. Infrared spectroscopy offers multiple advantages for serum analysis, such as reagent-free testing and the ability to quickly and directly measure multiple parameters simultaneously. This study collected serum samples from 66 healthy subjects to explore the relationship between dried serum infrared spectra and biochemical parameters, and to investigate the feasibility of simultaneously quantifying nine major serum components using dried serum infrared spectra. Initially, correlation analysis was conducted between spectral data and biochemical parameters, and the correlation spectral bands of glucose, protein and lipid were determined according to the correlation results. Subsequently, the interval random frog (IRF) algorithm was utilized to select the optimal characteristic wavenumbers of the correlated spectral bands, extracting the most informative spectral variables and constructing partial least squares (PLS) quantitative models. This method successfully achieved rapid and accurate quantification of nine major components in serum, including glucose, total protein, albumin, apolipoprotein A1, apolipoprotein B, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The experimental results showed that the correlation coefficient (Rp) range in the test set was 0.8892–0.9941. Among them, the quantification of total cholesterol yielded the highest Rp, corresponding to a root mean square error (RMSEP) of 7.2425 mg/dL in the test set, while the quantification of glucose yielded the lowest Rp, with an associated RMSEP of 2.3683 mg/dL. The Correlation Analysis (CA)-IRF-PLS method developed in this study outperformed the conventional PLS method, the direct use of the successive projection algorithm (SPA)-PLS quantitative method and other reported quantitative techniques, providing a novel approach for the real-time determination of clinical parameters in serum

Association analyses of nutritional markers with Parkinson’s disease and Alzheimer’s disease

IntroductionParkinson’s disease (PD) and Alzheimer’s disease (AD) are common neurodegenerative diseases with multifaceted etiology. Nutritional and metabolic abnormalities are frequently implicated in PD and AD. In this observational study, we analyzed a series of nutritional markers, and aimed to understand their association with AD and PD risk. MethodsA total of 424 PD patients, 314 AD patients, and 388 healthy controls were included. Nutritional markers including Hemoglobin A1c, vitamin B12, folate, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, total cholesterol (TC), uric acid and homocysteine (HCY) were measured. Significance for odds ratios examining was P < 0.0045 after bonferroni correction. ResultsMultifactor risk analysis showed that ApoB, LDL, and TC reduce PD risk, while HCY increase PD risk. ApoA1 and HCY are protective and risk factors for AD, respectively. ConclusionThe cross-sectional study demonstrates that HCY and lipid metabolism markers are associated with PD and AD risks. Our findings support the involvement of one-carbon metabolism and lipid metabolism disturbance in PD and AD.

Natural Honey Proteins Prevent Diet-Induced Obesity and Metabolic Disorders in Rats.

Previous studies have shown that oral whole honey reduces weight gain in rats on a normal diet (ND) or high-fat diet (HFD) and suppresses inflammation by modulating immunological cytokines in human neutrophils and macrophages. We hypothesize that the honey proteins (HP) are responsible for the reduced weight gain in rats on ND and HFD and that HP would alleviate obesity parameters. To test this, proteins were isolated from acacia honey through the salting-out method. Wistar rats (N = 24) were randomized to get ND or HFD for 4 weeks, then further randomized to four groups and treated with HP or saline for another 4 weeks. Energy intake (EI), body weight gain, EI per gram body weight gain, serum glucose, and lipids were measured. Expression of adipose tissue genes fatty acid binding protein (FABP), lipase C (LIPC), and apolipoprotein A-1 (APOA1) was evaluated through the quantitative polymerase chain reaction. HFD increased the body weight versus ND in weeks 1-4. HP for the next 4 weeks reduced weight gain in ND-HP and HFD-HP groups versus saline controls (P < .01). EI was not significantly different among groups. However, EI per gram body weight gain among groups was markedly different (P < .01), demonstrating reduced weight gain efficiency by HP (P < .01). HP reduced glucose in ND but not in HFD groups. Triglycerides were lower in both HP groups. The expressions of FABP, LIPC, and APOA1 genes were significantly increased (P < .05) in HP-treated HFD rats. Collectively, weight gain efficiency was remarkably reduced without altering EI in rats following the HP treatment, suggesting HP increased metabolic rate or substrate partitioning. Studies of HP are suggested in humans.

Evaluation of serum apolipoprotein concentrations and atherogenic indices in menopausal and premenopausal women in Nkwelle-Ezunaka

Background of study: The hormonal change in menopause affects lipid metabolism which could lead to dyslipidaemia, a risk factor for cardiovascular disease. Aim of study: To evaluate the levels of apolipoprotein A1, apolipoprotein B, Castelli risk index-1, Castelli risk index-11, atherogenic index of plasma and atherogenic coefficient in menopausal and premenopausal women. Materials and Methods: In this cross-sectional study ninety females were selected which consisted of 45 premenopausal, and 45 menopausal women using simple random sampling technique. Levels of apolipoprotein A1 and B were determined spectrophotometrically using enzyme linked immunosorbent assay (ELISA). Atherogenic indices were calculated with their respective formulas. Results: There was no significant difference in the mean levels of apo B (134.83±28.90 vs 130.73±30.55; p&gt;0.05), apo A1, atherogenic index of plasma, Castelli risk index-1, Castelli risk index-11 and atherogenic coefficient in the menopausal women compared with the premenopausal women but the mean values of both groups were outside the normal range of apo B, Castelli risk index-1, atherogenic index of plasma and atherogenic coefficient. Conclusion: Apo B, atherogenic index of plasma, Castelli risk index-1 and atherogenic coefficient are better indicators of cardiovascular risk.

Geospatial clustering of auto-antibodies against apolipoprotein A-1, heavy metals, cardiovascular and liver diseases in the general population

Abstract Aims Heavy metals (HM) are combustion-related environmental factors predisposing to cardiovascular (CVD), autoimmune and liver diseases, even below regulatory concentrations. Pro-atherogenic and pro-steatotic auto-antibodies against apolipoprotein A1 (AAA1) are prevalent in the general population for unclear reasons. We explored a putative interplay between HM exposure, AAA1, CVD risk factors and a non-alcoholic fatty liver disease (NAFLD) risk score, using a geospatial clustering approach at the general population level. Methods Getis-Ord, Moran I2 clustering and geographically weighted regression (GWR) geosptatial analyses were carried out on 6361 individuals recruited in the CoLaus/PsyCoLaus general population cohort. Geospatial dependences between serum AAA1, urinary HM (cadmium, arsenic, cobalt) concentrations, SCORE2 CVD risk, and fatty liver index (FLI) were assessed. Results Cadmium and cobalt were found to be associated with higher SCORE2 risk (p&amp;lt;0.04). AAA1 were associated with higher cadmium, cobalt, and cigarette consumption, independently of SCORE2 (p&amp;lt;0.04). AAA1 hotspots overlapped significantly with those of cadmium and FLI, independently of SCORE2. According to GWR, correlations between cadmium and AAA1 were the highest in railways proximity regions, increasing up to 10-fold compared to global associations. AAA1 were not associated with other HM. Conclusions These geospatial footprints highlight independent associations between Cadmium, AAA1, and NAFLD risk score in the general population. We hypothesize that environmental cadmium exposure may facilitate the occurrence of AAA1 in humans. Ongoing experimental studies will confirm/refute a possible causal link. Whether AAA1 could represent an early biological signature of cadmium exposure and subsequent health hazards remains to be shown.

Beneficial effects of hydroxychloroquine on blood lipids and glycated haemoglobin: A randomised interventional study in patients with rheumatoid arthritis and systemic lupus erythematosus.

Hydroxychloroquine (HCQ) exerts a large reduction of cardiovascular risk in patients with inflammatory diseases, but the mechanisms are not fully known. The aim of this study was to study potential mechanisms for this. This interventional study (EudraCT 2014-005418-45) in 30 patients (23 with rheumatoid arthritis, 7 with systemic lupus erythematosus) investigates the effects of HCQ on cardiovascular risk factors and arterial stiffness in patients with inflammatory disease. Blood lipids, blood pressure, blood glucose, glycated haemoglobin (HbA1c) and arterial stiffness was assessed at initiation, after four weeks of treatment and after eight weeks of treatment with 200 mg HCQ daily. After four weeks of treatment with HCQ, total cholesterol had decreased from 5.4 mmol/L to 5.1 mmol/L (p<0.001), low-density lipoproteins from 3,0 mmol/L to 2.7 mmol/L (p<0.001) and apolipoprotein B from 0.96 g/L to 0.90 g/L (p<0.01). Those levels remained unchanged after eight weeks of treatment with HCQ. Levels of triglycerides, high-density lipoproteins and apolipoprotein A1 remained unchanged during the study. HbA1c decreased in most patients, especially in patients with high levels at start of HCQ, but increased HbA1c was seen in patients with low levels at start of treatment with HCQ. No significant effect was seen on blood pressure or any measure of arterial stiffness. This study does not identify the mechanisms of cardiovascular risk reduction from HCQ. Arterial stiffness is not affected by HCQ. The impact of HCQ on HbA1c and blood lipids is rapid, but of modest magnitude, and these effects do not fully explain the reduced risk of cardiovascular disease seen in observational studies. The mechanisms of cardiovascular risk reduction from HCQ are yet not completely known.

Non-lipid metabolomic biomarkers are associated with adverse cardiac remodelling and cardiovascular outcomes

Abstract Background Metabolomics is the detailed profiling of circulating metabolites including carbohydrates, lipids, amino and fatty acids, and ketones, all of which are substrates used in energy metabolism by cardiomyocytes. Purpose The role of cholesterol fractions with cardiovascular risk is well-established. This novel study examines the association between non-lipid circulating metabolites and markers of cardiac remodelling as assessed by cardiovascular magnetic resonance (CMR) imaging. Metabolites associated with adverse remodelling were taken forward to examine their impact on incident cardiovascular disease (CVD); ischaemic heart disease (IHD) and heart failure (HF). Methods This study used data from the UK Biobank. After exclusions (prevalent IHD, HF; outliers), there were a maximum of 34,727 individuals for CMR analyses and 262,536 individuals for incident CVD analysis. For CMR analyses, outcome variables were LV end-diastolic volume (EDV), LV mass, LV mass:volume ratio (MVR), LV global longitudinal strain (GLS) and native T1. Separate regression models were built for each of the 40 scaled metabolite biomarkers. Each model incorporated one metabolite at a time with additional covariates: age, sex, ethnicity, systolic blood pressure, cholesterol medication use, type 2 diabetes, dietary intake, smoking status, fasting time, and time between recruitment and CMR examination. A Bonferroni-corrected significance threshold of 2.4x10-4 was used. To account for correlation between metabolites, Lasso regression with 10 fold cross-validation to identify the most important predictors was performed for LV MVR, LV GLS and native T1 whereby all metabolites and above covariates were included in the model. Metabolite predictors of adverse remodelling were included in an adjusted logistic regression model with incident CVD as an outcome. Results Metabolites demonstrating significant (p &amp;lt; 2.4x10-4) associations with CMR parameters are presented in Fig 1. For higher LV MVR and more positive LV GLS, the metabolites with the largest effect were monounsaturated fatty acids and glycoprotein acetyls. Higher omega-6:omega-3 ratio was associated with higher T1 values. The Lasso model identified 8 important predictors for adverse cardiac remodelling. Of these, two were routine biomarkers (creatinine, glucose). Of the remainder, monounsaturated fatty acids, glycoprotein acetyls and apolipoprotein B:apolipoprotein A1 ratio were significantly associated with increased risk of incident CVD (Fig 2). Current evidence regarding monounsaturated fatty acids in CVD is mixed. Glycoprotein acetyls are implicated in vascular inflammation. Apolipoproteins are thought to be a potential therapeutic target for CVD risk reduction. Conclusion This study demonstrates a role of non-lipid metabolites on subclinical CVD as assessed by adverse remodelling with CMR as well as associations with incident CVD. We highlight potential novel biomarkers for identification of CVD.Metabolite association with LV MVR/GLSMetabolite association with incident CVD

Unusual Mild Phenotype Presentation in an Elderly Patient with Homozygous Tangier Disease

Tangier disease (TD) is an extremely rare inherited disorder involving lipoprotein metabolism and high-density lipoprotein (HDL) recycling in particular. TD is linked with a mutation of the ABCA1 gene codifying for the transport protein ABCA1 which, in normal conditions, enables the efflux of cholesterol through the cell membrane to HDL and apolipoprotein A1. As such, early cardiovascular events and neuropathy are common in these patients, mostly in homozygous carriers. Here, we describe the unique case of a homozygous TD patient whose diagnosis was made in later life. He was affected by the A1046D protein mutation and suffered from mild neurological symptoms and asymptomatic atherosclerosis.

Alteration of the gut microbiota changes during the one-year Antarctic deployment in a group of Chinese Han population

BackgroundIt is common knowledge that people’s intestinal microbiota is significantly influenced by the external environment. Although the Antarctic continent has been discovered for nearly 200 years, it is still unclear how this environment affects the human intestinal microbiota, especially that of the Chinese Han population.MethodsTwelve explorers underwent a one-year Antarctic deployment from December 2017 to December 2018. The gut microbiota and clinical indexes at five time points, including two months (T1), five months (T2), eight months (T3), 11 months (T4) of residence in Antarctica and 7 months after returning to China (T5), were investigated.ResultsThe intestinal microbiota of the participants was changed after one-year Antarctic deployment even after they left Antarctica. For the microbiota tested after returning to China (T5), the amount of Citrobacter, Akkermansia and conditional pathogens such as Escherichia-Shigella increased significantly (P < 0.05). The concentration of the major biochemical indicators in the serum exhibited an increasing trend before T3, and decreased significantly at T4. When tested again at T5, most of the serum concentrations increased, only 5-hydroxytryptamine was significantly decreased. Spearman correlation analysis showed the change in the relative abundance of Anaerotruncus was negatively associated with the changes in the concentration of total thyroxine, alanine transaminase, γ-glutamyl transpeptidase, serum cystatin C and apolipoprotein A1. The relative abundance change in Citrobacter was positively associated with the change in the concentration of uric acid.ConclusionBy objectively analyzing the influence of the Antarctic environment on the change of intestinal microbiota, we were able to provide theoretical support for subsequent Antarctic related research.

Ce-MOF@Au-Based Electrochemical Immunosensor for Apolipoprotein A1 Detection Using Nanobody Technology.

Apolipoprotein A1 (Apo-A1) is a well-recognized biomarker in tissues, closely associated with cardiovascular diseases such as atherosclerosis, coronary artery disease, and heart failure. However, existing methods for Apo-A1 determination are limited by costly equipment and intricate operational procedures. Given the distinct advantages of electrochemical immunosensors, including affordability and high sensitivity, along with the unique attributes of nanobodies (Nbs), such as enhanced specificity and better tissue permeability, we developed an electrochemical immunosensor for Apo-A1 detection utilizing Nb technology. In our study, Ce-MOF@AuNPs nanocomposites were synthesized by using ultrasonic methods and applied to modify a glassy carbon electrode. The Nb6, screened from an Apo-A1 immunized phage library, was immobilized onto the nanocomposite material, establishing a robust binding interaction with Apo-A1. The recorded peak current values demonstrated a logarithmic increase corresponding to Apo-A1 concentrations ranging from 1 to 100,000 pg/mL, with a detection limit of 36 fg/mL. Additionally, the developed immunosensors demonstrated high selectivity, good stability, and reproducibility. Our methodology was also effectively utilized for serum sample analysis, showing good performance in clinical assessments. This electrochemical immunosensor represents a promising tool for Apo-A1 detection, with significant potential for advancing cardiovascular disease diagnostics.

Exploration of Risk Factors for Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Retrospective Study.

Patients with rheumatoid arthritis (RA) have increased mortality and morbidity rates owing to cardiovascular diseases (CVD). Timely detection of CVD in RA can greatly improve patient prognosis; however, this technique remains challenging. We aimed to investigate the risk factors for CVD incidence in patients with RA. This retrospective study included RA patients without CVD risk factors (n = 402), RA with CVD risk factors (n = 394), and RA with CVD (n = 201). Their data on routine examination indicators, vascular endothelial growth factor (VEGF), and immune cells were obtained from medical records. The characteristic variables between each group were screened using univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and logistic regression (LR) models, and individualized nomograms were further established to more conveniently observe the likelihood of CVD in RA. Univariate analysis revealed significantly elevated levels of white blood cells (WBC), blood urea nitrogen (BUN), creatinine, creatine kinase (CK), lactate dehydrogenase (LDH), VEGF, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), apolipoprotein B100 (ApoB100), and apolipoprotein E (ApoE) in RA patients with CVD, whereas apolipoprotein A1 (ApoA1) and high-density lipoprotein/cholesterol (HDL/TC) were decreased. Furthermore, the ratio of regulatory T (Treg) cells exhibiting excellent separation performance in RA patients with CVD was significantly lower than that in other groups, whereas the ratios of Th1/Th2/NK and Treg cells were significantly elevated. The LASSO, RF, and LR models were also used to identify the risk factors for CVD in patients with RA. Through the final selected indicators screened using the three machine learning models and univariate analysis, a convenient nomogram was established to observe the likelihood of CVD in patients with RA. Serum lipids, lipoproteins, and reduction of Treg cells have been identified as risk factors for CVD in patients with RA. Three nomograms combining various risk factors were constructed to predict CVD occurring in patients with RA (RA with/without CVD risk factors).

The Effect of Urinary Polycyclic Aromatic Hydrocarbon Metabolites on Lipid Profiles: Does Oxidative Stress Play a Crucial Mediation Role?

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites are associated with oxidative stress; however, epidemiological studies have not reported the impacts of these urinary PAH metabolites on blood lipid levels. This study investigated the relationship between urinary PAH metabolites, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and blood lipid profiles. A total of 109 elderly volunteers were recruited with complete datasets for analysis. Blood and morning urine samples were collected in the winter of 2011. The PAH metabolites, creatinine, and 8-OHdG levels in urine samples were analyzed using Gas Chromatography-Mass Spectrometry, spectrophotometry, and an ELISA kit, respectively. The blood lipid profiles were analyzed using an automatic biochemical analyzer. The relationship between lipid profiles and 8-OHdG was assessed using a two-independent sample nonparametric test, categorized by gender, smoking, and alcohol consumption status. After normalizing the concentration values, a general linear regression model was employed to examine the correlations between PAH metabolites, 8-OHdG, and lipid profiles. A mediation model was developed to investigate the mediating effect of 8-OHdG on the relationship between PAH metabolites and lipid profiles. The median of eight PAH metabolite concentrations in urine samples ranged from 1 to 10 μmol/mol creatinine (Cr). Significant differences in lipid profiles were observed across genders. However, no significant differences were found in smoking or alcohol consumption status for both genders. Linear regression analysis revealed that an increase in the logarithmic concentration of 2-hydroxynaphthalene (2-OHNap), 9-hydroxyfluorene (9-OHFlu), 3-hydroxyfluorene (3-OHFlu), 2-hydroxyfluorene (2-OHFlu), 1-hydroxypyrene (1-OHPyr), and 6-hydroxychrysene (6-OHChr) was associated with an increase in urinary 8-OHdG levels, after adjusting for BMI and age. Specifically, 1-hydroxynaphthalene (1-OHNap) and 1-OHPyr correlated negatively with apolipoprotein A1 (Apo A1). Conversely, 1-OHPyr was positively correlated with low-density lipoprotein cholesterol (LDL-C). In addition, b,c-dihydroxyphenanthrene (2-OHBcPhe) was positively associated with apolipoprotein B (Apo B). Notably, 8-OHdG did not exhibit a significant correlation with lipid profiles. The mediating effect of 8-OHdG on the relationship between hydroxylated PAHs and lipid profiles was not statistically significant. However, the indirect effects of hydroxylated PAHs on blood lipids were statistically substantial, specifically for 1-OHNap to Apo A1 (-0.025, 95% CI: -0.041, -0.009), 1-OHPyr to LDL-C (0.107, 95% CI: 0.011, 0.203), and 2-OHBcPhe to Apo B (0.070, 95% CI: 0.005, 0.135). This study suggests that an increase in urinary PAH metabolites may elevate the levels of urinary 8-OHdG and influence blood lipid profiles. However, no direct relationship was found between 8-OHdG and lipid profiles. The mediation analysis indicated that the effects of PAH metabolites on lipid changes may operate through pathways other than oxidative stress.

Mediation effect analysis of lipoprotein levels on BMI and cardiovascular outcomes in patients with heart failure

BackgroundAmong heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox.MethodsThe study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints.ResultsIn MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p<0.001, obese vs underweight), cardiovascular mortality (HR=0.46, 95%CI 0.30~0.73, p<0.001, obese vs underweight) and the incidence of MACCEs (HR=0.68, 95%CI 0.53~0.88, p=0.003, obese vs underweight). Mediation analysis revealed that TG was the strongest mediator between BMI and endpoints, with proportions of mediated effects of 6.6% (95%CI 2.2%~18.0%, p=0.0258, in all-cause death),7.0% (95%CI 2.3%~18.9%, p=0.0301, in cardiovascular death) and 10.2% (95%CI 3.3%~27.4%, p=0.0185, in MACCEs).ConclusionsThere is an "obesity paradox" in patients with heart failure, and lipoprotein levels especially triglyceride mediate the association between BMI and cardiovascular outcomes.