apoA-I Levels Research Articles

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.

The effect of medroxyprogesterone acetate on apolipoproteins and lipoprotein(a) concentrations in postmenopausal women: a meta-analysis of randomized controlled trials.

In view of the favorable effect of hormone replacement therapy (HRT) on the lipid profile in postmenopausal women, and the discrepancies that exist on the effect of medroxyprogesterone acetate (MPA) on lipoprotein concentrations and cardiovascular disease (CVD) risk, we conducted this meta-analysis of randomized controlled trials (RCT) to assess the efficacy of MPA on apolipoprotein and lipoprotein(a) concentrations in healthy postmenopausal women. A systematic search was conducted across multiple databases, including for English-language papers published up to September 2023 comparing the effect of MPA on ApoA-I, Apo-AII, and Lp(a) levels with those of a control group. A meta-analysis was conducted using a random-effects model, reporting the results as the weighted mean difference (WMD) with a 95% confidence interval (CI). The current meta-analysis included 11 publications. the comprehensive findings indicated a noteworthy reduction in ApoA-I (WMD:-8.70mg/dL,95%CI: -12.80, -4.59,P<0.001), a significant increase in Lp(a) concentrations (WMD: 1.36mg/dL, 95% CI: 0.10, 2.63, P=0.033), and a non-significant increase in ApoB concentrations (WMD: 0.57mg/dL, 95%CI: -1.25, 2.40, P=0.539) after the administration of MPA in postmenopausal women. In addition, a significant reduction in ApoB levels was identified in studies with a mean participant BMI ≥25kg/m2 (WMD: -4.94mg/dL, 95%CI: -5.71 to -4.18,P< 0.001) and a greater impact on ApoA-1 and Lp(a) levels was observed in trials with doses of 5mg/day compared with 2.5mg/day. MPA administration resulted in a significant increase in Lp(a) and decrease in ApoA-I levels and a non-significant increase in ApoB levels in healthy postmenopausal women.

Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.

Persistent infection with hepatitis B virus (HBV) often leads to disruptions in lipid metabolism. Apolipoprotein AII (apoAII) plays a crucial role in lipid metabolism and is implicated in various metabolic disorders. However, whether HBV could regulate apoAII and contribute to HBV-related dyslipidemia and the underlying mechanism remain unclear. This study revealed significant reductions in apoAII expression in HBV-expressing cell lines, the serum, and liver tissues of HBV-transgenic mice. The impact of HBV on apoAII is related to small hepatitis B virus surface antigen (SHBs). Overexpression of SHBs decreased apoAII levels in SHBs-expressing hepatoma cells, transgenic mice, and the serum of HBV-infected patients, whereas suppression of SHBs increased apoAII expression. Mechanistic investigations demonstrated that SHBs repressed the apoAII promoter activity through a HNF4α- and C/EBPγ-dependent manner; SHBs simultaneously upregulated C/EBPγ and downregulated HNF4α by inhibiting the PI3K/AKT signaling pathway through activating endoplasmic reticulum (ER) stress. Serum lipid profile assessments revealed notable decreases in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) in SHBs-transgenic mice compared to control mice. However, concurrent overexpression of apoAII in these mice effectively counteracted these reductions in lipid levels. In HBV patients, SHBs levels were negatively correlated with serum levels of HDL-C, LDL-C, TC, and TG, whereas apoAII levels positively correlated with lipid content. This study underscores that SHBs contributes to dyslipidemia by suppressing the PI3K/AKT pathway via inducing ER stress, leading to altered expression of HNF4α and C/EBPγ, and subsequently reducing apoAII expression.IMPORTANCEThe significance of this study lies in its comprehensive examination of how the hepatitis B virus (HBV), specifically through its small hepatitis B virus surface antigen (SHBs), impacts lipid metabolism-a key aspect often disrupted by chronic HBV infection. By elucidating the role of SHBs in regulating apolipoprotein AII (apoAII), a critical player in lipid processes and associated metabolic disorders, this research provides insights into the molecular pathways contributing to HBV-related dyslipidemia. Discovering that SHBs downregulates apoAII through mechanisms involving the repression of the apoAII promoter via HNF4α and C/EBPγ, and the modulation of the PI3K/AKT signaling pathway via endoplasmic reticulum (ER) stress, adds critical knowledge to HBV pathogenesis. The research also shows an inverse correlation between SHBs expression and key lipid markers in HBV-infected individuals, suggesting that apoAII overexpression could counteract the lipid-altering effects of SHBs, offering new avenues for understanding and managing the metabolic implications of HBV infection.

Lipid Metabolism Disorders as Diagnostic Biosignatures in Sepsis.

Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in human sepsis. ApoA-IV (analyzed in 156 patients with systemic inflammatory response syndrome (SIRS)/sepsis) and cholesteryl ester (CE) (analyzed in 121 of these patients) were lower in patients compared to 43 healthy controls. In contrast, triglyceride (TG) levels were elevated in patients. ApoA-IV levels in plasma of the patients did not correlate with these lipids. Patients with SIRS, sepsis or septic shock had comparable apoA-IV, TG, CE and free cholesterol (FC) levels. Patients on dialysis had significantly lower CE levels, whereas apoA-IV levels did not change much. CE levels were elevated in patients with viral sepsis due to SARS-CoV-2 infection in comparison to SIRS/sepsis patients not infected by this virus. CE levels correlated negatively with procalcitonin, interleukin-6 and bilirubin, while TGs were positively associated with bilirubin and C-reactive protein. ApoA-IV, TG, CE and FC levels were not associated with bacterial infection or survival. In conclusion, this analysis suggests that CE levels decline in sepsis-related renal failure and also shows that plasma apoA-IV and CE levels are early biomarkers of sepsis.

Association of cerebrospinal fluid NPY with peripheral ApoA: a moderation effect of BMI

BackgroundApoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB.MethodsIn this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured.ResultsIn the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, β=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04).ConclusionThis study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease.

Divergent Roles of APOAI and APOM in the Identification of Alcohol Use Disorder and Their Association With Inflammation and Cognitive Decline: A Pilot Study.

Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition. A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n = 33; 72.7% men) and healthy controls (n = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated. Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample. The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline.

Differential distribution of plasma apoA-I and apoB levels and clinical significance of apoB/apoA-I ratio in ischemic stroke subtypes.

Ischemic stroke (IS) is classified into clinical subtypes and likely influenced by various lipid components. Nevertheless, the roles of apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and apoB/apoA-I ratio in different IS subtypes remain underexplored. This study aimed to investigate the differential distribution of plasma apoA-I and apoB levels among IS subtypes and to evaluate the predictive value of the apoB/apoA-I ratio in assessing IS subtypes and disease severity. In this study, 406 IS patients were categorized into three IS-subtypes based on clinical manifestations and imaging assessment, including intracranial atherosclerosis-related IS patients (ICAS, n = 193), extracranial atherosclerosis-related IS patients (ECAS, n = 111), and small artery occlusion-related IS patients (SAO, n = 102). Plasma apoA-I and apoB levels were measured upon hospital admission. Random forest (RF) models were performed to assess predictive values of these apolipoproteins apoB, apoA-I and their ratio in assessing IS subtype stratification and disease severity. Serum apoA-I levels were significantly lower in ICAS compared to ECAS and SAO patients (p < 0.0001), while apoB levels were higher in ICAS patients (p < 0.0001). The apoB/apoA-I ratio was significantly higher in ICAS compared to ECAS and SAO patients (p < 0.0001). Correlation analyses found a significant correlation between the apoB/apoA-I ratio and conventional lipid components. Additionally, RF models and plots of variable importance and distribution of minimal depth revealed that the apoB/apoA-I ratio played the most influential predictor in predicting IS subtypes and stenosis severity. Our study shows the differential distribution of apoA-I and apoB IS subtypes and reveals the significance of the apoB/apoA-I ratio in assessing IS subtypes and arterial stenosis severity. Further studies are warranted to validate these findings and enhance their clinical applicability.

Assessment of cardiac function in farmers occupationally exposed to pesticides in gboko local government area, benue state

Any compound or combination of substances meant to prevent, eradicate, repel, or mitigate any pest is known as a pesticide. Despite the benefits of using pesticides for pests, weeds, and disease control, there have been concerns about adverse effects of these compounds on the human health. This cross-sectional study was designed to assess the cardiac function of farmers occupationally exposed to pesticides, in Gboko Local Government Area, Benue State, Nigeria.One hundred ten (110) participants comprising 70 farmers and 40 controls were recruited for the study using a multi-stage random sampling technique. They were aged between 20-60 years and were age-matched. Five (5) ml of fasting blood samples were collected from each participant for the determination of Apolipoprotein A1 (ApoA1), Apolipoprotein B-100 (ApoB100) and Troponin I level using standard laboratory methods. Also, the body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the participants were also determined. The results showed significantly lower mean BMI (23.02±3.94 Vs 24.94±3.12; p= 0.031) and serum ApoA1 (150.73±13.52 Vs 167.27±15.65; p=0.024) while the mean SBP (140.49±19.34 Vs 119.75±10.30; p=0.000), DBP (82.86±12.16 Vs 77.53±7.76; p=0.014) and mean serum Troponin-I (3.11±5.46 Vs 1.38±0.15; p=0.049) levels were significantly higher in the farmers compared to control respectively. However, there was no significant difference in the mean serum ApoB-100 level in the farmers when compared to the control group (p=0.104). : This study showed that the farmers had lower body mass index and higher serum levels of apoA-I, apoB-100, and Troponin I, as well as systolic and diastolic blood pressure, as compared to the control group. Nonetheless, in both the test and control groups, these results fell within the typical reference ranges. Further longitudinal research is required to gain a deeper understanding of the effects of pesticide exposure on cardiac function in farmers.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Effect of a Dietary Supplement Containing Dry Artichoke and Bergamot Extracts on Metabolic and Vascular Risk Factors in Individuals with Suboptimal Cholesterol Levels.

The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke-both standardized in their characteristic polyphenolic fractions-could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo (p < 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders.

The association of circulating lipoprotein lipids and apolipoproteins with risk of endometriosis: a Mendelian randomization study.

Endometriosis is a poorly understood disease that affects up to 196 million women worldwide and imposes high costs in terms of economic burden and quality of life of women. Traits of circulating lipids have been related to the onset and progression of endometriosis in previous observational studies but the results have remained contradictory. We performed univariable and multivariable Mendelian randomization (MR) analyses using instrument variables to genetically predict the associations of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoprotein (apo) A-I and B from the UK Biobank with endometriosis (consisting of 8288 cases and 68 969 controls from the FinnGen consortium). The inverse-variance weighted (IVW) method was used as the primary estimate, whereas MR-Egger and weighted median were conducted as complements to the IVW model. Increased levels of triglycerides were associated with higher risk of endometriosis and endometriosis of the pelvic peritoneum in the univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, triglycerides still retained a robust effect. Decreased levels of apoA-I and HDL cholesterol were associated with increased risk of endometriosis and endometriosis of the pelvic peritoneum in univariable MR analyses. After mutual adjustment, HDL cholesterol retained a robust effect whereas the association for apoA-I was attenuated. This is the first MR-based evidence to suggest that triglycerides and HDL cholesterol are the predominant traits that account for the aetiological relationship of lipoprotein lipids with risk of endometriosis, in particular endometriosis of the pelvic peritoneum. Further well-designed randomized controlled trials are needed to address these results.

Circulating lipids, lipid-lowering drug targets, and breast cancer risk: Comprehensive evidence from Mendelian randomization and summary data-based Mendelian randomization.

Breast cancer (BC) is the most common and fatal cancer among women, yet the causal relationship between circulating lipids, lipid-lowering drugs, and BC remains unclear. Mendelian randomization (MR) and summary data-based MR (SMR) analysis are used to explore the causal relationship between plasma lipids, lipid-lowering drug targets, and BC. The result of MR suggested that per mg/dL higher levels of LDL-C (OR = 1.045, FDR = 0.023), HDL-C (OR = 1.079, FDR = 0.003), TC (OR = 1.043, FDR = 0.026), and APOA-I (OR = 1.085, FDR = 2.64E-04) were associated with increased BC risk, while TG was associated with reduced BC risk (OR = 0.926, FDR = 0.003). Per mg/dL higher levels of HDL-C (OR = 1.080, FDR = 0.011) and APOA-I (OR = 1.083, FDR = 0.002) were associated with increased ER+BC risk, while TG was associated with reduced ER+BC risk (OR = 0.909, FDR = 0.002). For every per 1mg/dL decrease in LDL, HMGCR (OR: 0.839; FDR = 0.016), NPC1L1 (OR: 0.702; FDR = 0.004), and PCSK9 (OR: 0.916; FDR = 0.026) inhibition were associated with reduced BC risk, whereas CETP inhibition (OR: 1.194; FDR = 0.026) was associated with increased BC risk. For every per 1mg/dL decrease in LDL, HMGCR (OR: 0.822; FDR = 0.023), NPC1L1 (OR: 0.633; FDR = 2.37E-03), and APOB inhibition (OR: 0.816; FDR = 1.98E-03) were associated with decreased ER-BC risk, while CETP inhibition (OR: 1.465; FDR = 0.011) was associated with increased ER-BC risk. SMR analysis indicated that HMGCR was associated with increased BC risk (OR: 1.112; p = 0.044). Lipids are associated with the BC risk, and lipid-lowering drugs targets HMGCR, NPC1L1, PCSK9, and APOB may be effective strategies for preventing BC. However, lipid-lowering drugs target CETP may potentially increase BC risk.

Investigating the Incidence of Dyslipidemia among Brazilian Children and Adolescents Diagnosed with Type 1 Diabetes Mellitus: A Cross-Sectional Study.

The treatment of Type 1 Diabetes Mellitus (T1DM) has always been a challenge for health professionals in relation to glycemic control. Increased body fat has been related to a worsening of the lipid profile and increased prevalence of dyslipidemia in this population, leading to negative repercussions on the control of cardiovascular risk. We aimed to investigate the distribution of lipid levels and the presence of dyslipidemia in children and adolescents with T1DM. A cross-sectional observational study was conducted with 81 individuals of both sexes (4-19 years) diagnosed with T1DM. Anthropometric and biochemical data were collected, in addition to data on physical activity level, sexual maturation stage, and insulin administration regimen. Lipid levels were categorized as normal, borderline, and elevated, and the presence of dyslipidemia was diagnosed by the presence of one or more altered lipid parameter. We noted a prevalence of dyslipidemia in 65.4% of the participants when considering borderline lipid values. Of those, 23.5% had one altered lipid level, and 42.0% had two or more. The main altered lipid levels were total cholesterol and triglycerides, followed by non-HDL-c. The main factor associated with the worsening of lipid levels was the increase in HbA1c. Sex had a significant effect on the levels of TC, HDL-c, and ApoA-I. The results of this study reinforce the need to monitor lipid profile in children and adolescents with T1DM, as well as the importance of early intervention in treating dyslipidemia, especially in patients with poor glycemic control.

Chronic Real-Ambient PM2.5 Exposure Exacerbates Cardiovascular Risk via Amplifying Liver Injury in Mice Fed with a High-Fat and High-Cholesterol Diet.

Epidemiology has associated fine particulate matter (PM2.5) exposure with an increased cardiovascular risk. However, the underlying mechanism, particularly from the liver perspective, remains unclear. Here, the influence of chronic PM2.5 exposure on cardiovascular risk in mice fed a high-fat and high-cholesterol diet (HFCD) was studied by using a real-world PM2.5 exposure system. Results showed that PM2.5 exposure elevated the serum levels of nonhigh-density lipoprotein cholesterol (non-HDL-C) and oxidized low-density lipoprotein (oxLDL) in HFCD-fed mice, demonstrating increased cardiovascular risk. To investigate the molecular mechanism, lipidomics and metabolomics analyses were conducted and revealed that PM2.5 exposure enhanced lipid accumulation and disturbed purine metabolism and glutathione metabolism in the liver of HFCD-fed mice, contributing to the elevated non-HDL-C levels and intensified oxidative stress. Moreover, PM2.5 exposure increased total cholesterol levels by upregulating Hmgcr expression and downregulating Cyp7a1 expression in the livers of HFCD-fed mice. The HDL-C level was reduced by inhibiting the hepatic Abca1 and Abcg1 expression and decreasing the levels of ApoA-I and LCAT. Additionally, the PM2.5-induced pro-oxidative environment impeded the oxLDL clearance and further triggered inflammation, in turn exacerbating oxidative stress and oxLDL production. This study demonstrated a synergy of PM2.5 and HFCD on cardiovascular risk and illuminated the molecular mechanism in PM2.5-susceptible populations.

Bacterial lipopolysaccharide forms aggregates with apolipoproteins in male and female rat brains after ethanol binges

Alcohol binge drinking allows the translocation of bacterial lipopolysaccharide (LPS) from the gut to the blood, which activates the peripheral immune system with consequences in neuroinflammation. A possible access/direct signaling of LPS to/in the brain has not yet been described under alcohol abuse conditions. Apolipoproteins are compounds altered by alcohol with high affinity to LPS which may be involved in its transport to the brain or in its elimination. Here, we explored the expression of small components of LPS, in its free form or bound to apolipoproteins, in the brain of female and male rats exposed to alcohol binges. Animals received ethanol oral gavages (3 g/kg every 8 h) for 4 days. LPS or its components (Lipid A and core), LPS-binding protein, corticosterone, lipoproteins (HDL, LDL), apolipoproteins (ApoAI, ApoB, and ApoE), and their receptors were measured in plasma and/or in nonperfused prefrontal cortex (PFC) and cerebellum. Brain LipidA-apolipoprotein aggregates were determined by Western blotting and confirmed by co-immunoprecipitation. In animals exposed to alcohol binges: 1) plasma LPS-binding protein was elevated in both sexes; 2) females showed elevations in plasma ApoAI and corticosterone levels; 3) Lipid A formed aggregates with ApoAI in the female PFC and with ApoB in males, the latter showing Toll-like receptor 4 upregulation in PFC but not females. These results suggest that small bacterial components are present within the brain, forming aggregates with different apolipoproteins, depending on the sex, after alcohol binge intoxications. Results may have implications for the crosstalk between alcohol, LPS, and neuroinflammation.

Serum CircNIPSNAP3A is Associated with Metabolic Disorders, Atherosclerosis and Severity of Coronary Artery Disease in a Chinese Population.

The relationships of serum circNIPSNAP3A and circHIPK3 with metabolic disorders, atherosclerosis and severity of coronary artery disease (CAD) remain to be clarified. Three hundred and thirty-eight subjects were categorized into normal coronary artery, atherosclerosis and CAD groups. Clinical data including anthropometric indexes, medical history, and physiological and biochemical parameters were collected. Serum circNIPSNAP3A and circHIPK3 were determined by quantitative real-time PCR. CAD severity was evaluated by clinical manifestation, electrocardiogram and coronary angiography. Both CAD and atherosclerosis groups had a higher serum level of circNIPSNAP3A than the normal coronary artery group (P < 0.05 for all). The subjects with a high percentage (> 66th percentile) of circNIPSNAP3A had higher mean levels of triglycerides, uric acid and homocysteine, and lower mean levels of high-density lipoprotein cholesterol and apolipoprotein AI than those with a low percentage (< 33rd percentile) of circNIPSNAP3A. Notably, circNIPSNAP3A is significantly and independently associated with CAD, and subjects with a high percentage of circNIPSNAP3A had more diseased coronary branches and a higher incidence of acute coronary syndrome than those with a low percentage of circNIPSNAP3A. Regarding circHIPK3, subjects with a medium or high percentage of circHIPK3 had a lower mean level of apolipoprotein AI than those with a low percentage of circHIPK3, but no significant differences in the incidence and severity of CAD among the < 33rd, 33rd-66th, and > 66th percentiles of circHIPK3 were detected. Serum circNIPSNAP3A is related to cardiovascular risk factors and CAD severity, and may be a potential prognostic marker and/or therapeutic target for CAD.

Predictive value of lipoproteins on progression to chronic critical illness in intensive care unit patients

To explore the predictive value of lipoproteins on the progression of critically ill patients to chronic critical illness (CCI). A retrospective cohort study was conducted to analyze clinical data of patients admitted to the intensive care unit (ICU) of Nanjing Drum Tower Hospital from January 1, 2020, to December 31, 2022. The levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and apolipoproteins (ApoA-I, ApoB) at 1, 3, 7, 14 and 21 days after admission to ICU were collected. The progression to CCI was recorded. CCI was defined as the length of ICU stay ≥14 days with sustained organ dysfunction [sequential organ failure assessment (SOFA) score ≥2]. Differences in lipoprotein levels between the patients with and without CCI were compared. Multivariate Logistic regression was used to analyze risk factors for critically ill patients progressing to CCI. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of lipoproteins on critically ill patients progressing to CCI. A total of 200 patients were enrolled in the final analysis. 137 patients (68.5%) progressed to CCI, and 63 patients (31.5%) did not. The lipoprotein indicators in the CCI group showed a decrease after the acute phase, while the lipoprotein indicators in the non-CCI group showed an increase. The levels of HDL, LDL, ApoA-I, and ApoB at various time points in the CCI group were significantly lower than those in the non-CCI group. HDL at 7 days in the CCI group was significantly lower than that in the non-CCI group [mmol/L: 0.44 (0.31, 0.61) vs. 0.67 (0.49, 0.75), P < 0.01]. Multivariate Logistic regression analysis showed that 7-day HDL was an independent risk factor for critically ill patients progressing to CCI [odds ratio (OR) = 0.033, 95% confidence interval (95%CI) was 0.004-0.282, P = 0.002]. ROC curve analysis showed that the area under the ROC curve (AUC) of 7-day HDL for predicting critically ill patients progressing to CCI was 0.702, with a 95%CI of 0.625-0.779, P < 0.001. When the optimal cut-off value was 0.59 mmol/L, the sensitivity was 69.8%, and the specificity was 72.4%. The low level of lipoproteins is closely related to the progression of critically ill patients, and 7-day HDL has a certain predictive value for critically ill patients progressing to CCI. Continuously observation of the change trend of lipoprotein level is helpful to judge the progression of CCI in critically ill patients.

Pitavastatin treatment remodels the HDL subclass lipidome and proteome in hypertriglyceridemia

HDL particles vary in lipidome and proteome, which dictate their individual physicochemical properties, metabolism, and biological activities. HDL dysmetabolism in nondiabetic hypertriglyceridemia (HTG) involves subnormal HDL-cholesterol and apoAI levels. Metabolic anomalies may impact the qualitative features of both the HDL lipidome and proteome. Whether particle content of bioactive lipids and proteins may differentiate HDL subclasses (HDL2b, 2a, 3a, 3b, and 3c) in HTG is unknown. Moreover, little is known of the effect of statin treatment on the proteolipidome of hypertriglyceridemic HDL and its subclasses. Nondiabetic, obese, HTG males (n = 12) received pitavastatin calcium (4 mg/day) for 180 days in a single-phase, unblinded study. ApoB-containing lipoproteins were normalized poststatin. Individual proteolipidomes of density-defined HDL subclasses were characterized prestatin and poststatin. At baseline, dense HDL3c was distinguished by marked protein diversity and peak abundance of surface lysophospholipids, amphipathic diacylglycerol and dihydroceramide, and core cholesteryl ester and triacylglycerol, (normalized to mol phosphatidylcholine), whereas light HDL2b showed peak abundance of free cholesterol, sphingomyelin, glycosphingolipids (monohexosylceramide, dihexosylceramide, trihexosylceramide, and anionic GM3), thereby arguing for differential lipid transport and metabolism between subclasses. Poststatin, bioactive lysophospholipid (lysophosphatidylcholine, lysoalkylphosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylinositol) cargo was preferentially depleted in HDL3c. By contrast, baseline lipidomic profiles of ceramide, dihydroceramide and related glycosphingolipids, and GM3/phosphatidylcholine were maintained across particle subclasses. All subclasses were depleted in triacylglycerol and diacylglycerol/phosphatidylcholine. The abundance of apolipoproteins CI, CII, CIV, and M diminished in the HDL proteome. Statin treatment principally impacts metabolic remodeling of the abnormal lipidome of HDL particle subclasses in nondiabetic HTG, with lesser effects on the proteome.

Lipoprotein lipids and apolipoproteins in primary immune thrombocytopenia: Results from a clinical characteristics and causal relationship verification, potential drug target identification by Mendelian randomization analyses.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. Cellular and systemic lipid metabolism plays a significant role in the regulation of immune cell activities. However, the role of lipoprotein lipids and apolipoproteins in ITP remains elusive. The automatic biochemistry analyser was used to measure the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apoA-I), apoB, apoE and lipoprotein a [LP(a)]. Genetic variants strongly associated with circulating lipoprotein lipids and apolipoproteins (LDL-C, apoB, TG, HDL-C and apoA-I) were extracted to perform Mendelian randomization (MR) analyses. Finally, drug-target MR and passive ITP mice model was used to investigate the potential druggable targets of ITP. Levels of HDL-C, apoA-I, decreased and LP(a) increased in ITP patients compared with healthy controls. Low HDL-C was causally associated with ITP susceptibility. Through drug-target MR and animal modelling, ABCA1 was identified as a potential target to design drugs for ITP. Our study found that lipid metabolism is related to ITP. The causative association between HDL-C and the risk of ITP was also established. The study provided new evidence of the aetiology of ITP. ABCA1 might be a potential drug target for ITP.

Proteomic Determinants of Variation in Cholesterol Efflux: Observations from the Dallas Heart Study.

High-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood. Our goal was to identify and define key HDL-associated proteins that modulate CEC in humans. The proteomic signature of plasma HDL was quantified in 36 individuals in the multi-ethnic population-based Dallas Heart Study (DHS) cohort that exhibited persistent extremely high (>=90th%) or extremely low CEC (<=10th%) over 15 years. Levels of apolipoprotein (Apo)A-I associated ApoC-II, ApoC-III, and ApoA-IV were differentially correlated with CEC in high (r = 0.49, 0.41, and -0.21 respectively) and low (r = -0.46, -0.41, and 0.66 respectively) CEC groups (p for heterogeneity (pHet) = 0.03, 0.04, and 0.003 respectively). Further, we observed that levels of ApoA-I with ApoC-III, complement C3 (CO3), ApoE, and plasminogen (PLMG) were inversely associated with CEC in individuals within the low CEC group (r = -0.11 to -0.25 for subspecies with these proteins vs. r = 0.58 to 0.65 for subspecies lacking these proteins; p < 0.05 for heterogeneity). These findings suggest that enrichment of specific proteins on HDLs and, thus, different subspecies of HDLs, differentially modulate the removal of cholesterol from the vasculature.

Understanding the Relationship between Polycystic Ovarian Syndrome (PCOS) and Dyslipidemia

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder characterized by signs and symptom of androgen excess and ovarian dysfunction in the absence of other diagnosis, with a prevalence of ~6%-~20%. The aetiology of PCOS can either be unknown (primary) or originating from identifiable causes (secondary) like obesity, idiopathic hirsutism, epilepsy, androgen-secreting tumors etc. Weight gain especially around the stomach, missed, irregular or light menstruations, hyperandrogenism, infertility can serve as indicators for PCOS. This review is aimed at examining the relationship that exists between PCOS and dyslipidemia. With a prevalence report of about 70%, dyslipidemia, is related to PCOS, and its causes are multifactorial with many cases being undiagnosed due to different diagnostics criteria for PCOS. Studies revealed that women with PCOS showed increased levels of LDL-cholesterol, VLD Lipoprotein, ApoC-I, lipoprotein (a), decreased levels of HDL-cholesterol and ApoA-I while ApoB. Psychophysiology in dyslipidemia in PCOS include: obesity, hyperandrogenism. Insulin resistance. Diagnostic measures include: complete lipid profile test, pelvic ultrasound and transvaginal scan, hormone tests, glucose and insulin tolerance test, etc. There is no known cure of PCOS reported yet but there are different options on management which include lifestyle change, use of statin drugs if lifestyle modifications do not work, use of androgen inhibiting drugs and metformin might help. It is important and more advisable for the age range for PCOS testing to be reduced to accommodate females just entering puberty.