Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives

Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.

The difference of lipid profiles between psoriasis with arthritis and psoriasis without arthritis and sex-specific downregulation of methotrexate on the apolipoprotein B/apolipoprotein A-1 ratio

Background Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. Objective To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). Methods In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. Results Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. Conclusion PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. Trial registration ChiCTR2000036192

Loss-of-function mutation in Pcsk1 increases serum APOA1 level and LCAT activity in mice

Background The convertase subtilisin/kexin family 1 gene (PCSK1) has been associated in various human genetics studies with a wide spectrum of metabolic phenotypes, including early-onset obesity, hyperphagia, diabetes insipidus, and others. Despite the evident influence of PCSK1 on obesity and the known functions of other PCSKs in lipid metabolism, the role of PCSK1 specifically in lipid and cholesterol metabolism remains unclear. This study evaluated the effect of loss of PCSK1 function on high-density lipoprotein (HDL) metabolism in mice. Results HDL cholesterol, apolipoprotein A1 (APOA1) levels in serum and liver, and the activities of two enzymes (lecithin-cholesterol acyltransferase, LCAT and phospholipid transfer protein, PLTP) were evaluated in 8-week-old mice with a non-synonymous single nucleotide mutation leading to an amino acid substitution in PCSK1, which results in a loss of protein’s function. Mutant mice had similar serum HDL cholesterol concentration but increased levels of serum total and mature APOA1, and LCAT activity in comparison to controls. Conclusions This study presents the first evaluation of the role of PCSK1 in HDL metabolism using a loss-of-function mutant mouse model. Further investigations will be needed to determine the underlying molecular mechanism.

Risk Factors to Predict Ocular Metastasis in Older Adult Patients With Gastric Cancer:LDL, ApoA1, and CA724

Objective: The purpose of this study was to explore the risk factors for Ocular metastasis (OM) of Gastric cancer (GC). Methods: This is a retrospective cohort study. A total of 1165 patients with GC were enrolled in this study and divided into OM and non-ocular metastasis (NOM) groups. Chi-square and independent samples t tests were used to determine whether differences in demographic characteristics and serological indicators (SI) between the two groups were significant. In addition, binary logistic regression was used to analyze the value of various SI as risk factors for OM in patients with GC. The statistical threshold was set as P < .05. Finally, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of various SI in differentiating the occurrence of OM in patients with GC. Results: The incidence of OM in older adults with GC was 1.1%. Adenocarcinoma was the most common type of GC in both groups, and there was no significant difference in demographic characteristics between the groups. Low-density lipoprotein (LDL), carbohydrate antigen-724 (CA724), and carcinoembryonic antigen levels were significantly higher in the OM group than the NOM group, while those of apolipoprotein A1 (ApoA1) were significantly lower in the OM than the NOM group. Binary logistic analysis showed that LDL, ApoA1, and CA724 were independent risk factors for OM in patients with GC ( P < .001, P = .033, and P = .008, respectively). ROC curve analysis generated area under the curve (AUC) values of 0.881, 0.576, and 0.906 for LDL, ApoA1, and CA724, respectively. In addition, combined analysis of LDL, ApoA1, and CA724 generated the highest AUC value of 0.924 ( P < .001). Conclusion: Among SI, LDL, ApoA1, and CA724 have predictive value for the occurrence of OM in GC, with the three factors combined having the highest value.

The Relationship between Blood Lipids and Risk of Atrial Fibrillation: Univariable and Multivariable Mendelian Randomization Analysis

We performed univariable and multivariable Mendelian randomization (MR) analysis to evaluate the association between blood lipids and risk of atrial fibrillation (AF), including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), Apolipoprotein A1, and Apolipoprotein B. Methods: Data on the single nucleotide polymorphisms (SNPs) related to blood lipids were obtained from the UK Biobank study with more than 300,000 subjects of White British European ancestry, and data for AF were from the latest meta-analysis of Genome-wide association study (GWASs) with six independent cohorts with more than 1,000,000 subjects of European ancestry. The univariable MR analysis was conducted to explore whether genetic evidence of individual lipid-related traits was significantly associated with AF risks and multivariable MR analysis with three models was performed to assess the independent effects of lipid-related traits. Results: The IVW estimate showed that genetically predicted LDL-C (OR: 1.016, 95% CI: 0.962–1.073, p = 0.560), HDL-C (OR: 0.951, 95% CI: 0.895–1.010, p = 0.102), TG (OR: 0.961, 95% CI: 0.889–1.038, p = 0.313), Apolipoprotein A1 (OR: 0.978, 95% CI: 0.933–1.025, p = 0.356), and Apolipoprotein B (OR: 1.008, 95% CI: 0.959–1.070, p = 0.794) were not causally associated with the risk of AF. Sample mode (OR: 0.852, 95% CI: 0.731–0.993, p = 0.043) and weighted mode (OR: 0.907, 95% CI: 0.841–0.979, p = 0.013) showed that a 1-unit increase in TG (mmol/L) was causally associated with a 14.8% and 9.3% relative decrease in AF risk, respectively. The multivariable MR analysis with model 1, 2, and 3 indicated that TG, LDL-C, HDL-C, Apolipoprotein A1, and Apolipoprotein B were not associated with the lower risk for AF. Conclusions: Our multivariable Mendelian randomization analysis (MVMR) finding suggested no genetic evidence of lipid traits was significantly associated with AF risk. Furthermore, more work is warranted to confirm the potential association between lipid traits and AF risks.

An Analysis of Characteristics of Post-Stroke Fatigue in Patients without Depression: A Retrospective Chart Review

Post-stroke fatigue (PSF) is among the most common stroke sequelae and affects rehabilitation, resulting in poor recovery. A main influencing factor may be depression, which has been investigated with fatigue in several clinical trials. We aimed to evaluate the characteristics of fatigue in post-stroke patients without depression through a retrospective chart review. The medical records of stroke patients hospitalized in the Stroke and Brain Disease Center, Kyung Hee University Korean Medicine Hospital were reviewed. Stroke patients without depression were divided into a PSF group and control group (without fatigue). The demographic characteristics, type of stroke, medical history, laboratory examinations, clinical features, and pattern identification of each patient were recorded and compared between the study groups. The medical records of 216 patients were reviewed; 85 and 131 patients were assigned to the PSF and control group, respectively. Apolipoprotein A1 levels were significantly lower in the PSF than in the control group (105.6 ± 16.5 vs. 116.2 ± 21.8). We found a significantly higher occurrence of reversal cold of the extremities and a lower probability of fire-heat pattern in the PSF group than in the control group. This study suggests that apolipoprotein A1 levels are lower and cold manifestations are more common in PSF patients without depression than in those without fatigue.

Association Between Dietary Patterns and Plasma Lipid Biomarker and Female Breast Cancer Risk: Comparison of Latent Class Analysis (LCA) and Factor Analysis (FA)

Background: Diet research focuses on the characteristics of “dietary patterns” regardless of the statistical methods used to derive them. However, the solutions to these methods are both conceptually and statistically different.Methods: We compared factor analysis (FA) and latent class analysis (LCA) methods to identify the dietary patterns of participants in the Chinese Wuxi Exposure and Breast Cancer Study, a population-based case-control study that included 818 patients and 935 healthy controls. We examined the association between dietary patterns and plasma lipid markers and the breast cancer risk.Results: Factor analysis grouped correlated food items into five factors, while LCA classified the subjects into four mutually exclusive classes. For FA, we found that the Prudent-factor was associated with a lower risk of breast cancer [4th vs. 1st quartile: odds ratio (OR) for 0.70, 95% CI = 0.52, 0.95], whereas the Picky-factor was associated with a higher risk (4th vs. 1st quartile: OR for 1.35, 95% CI = 1.00, 1.81). For LCA, using the Prudent-class as the reference, the Picky-class has a positive association with the risk of breast cancer (OR for 1.42, 95% CI = 1.06, 1.90). The multivariate-adjusted model containing all of the factors was better than that containing all of the classes in predicting HDL cholesterol (p = 0.04), triacylglycerols (p = 0.03), blood glucose (p = 0.04), apolipoprotein A1 (p = 0.02), and high-sensitivity C-reactive protein (p = 0.02), but was weaker than that in predicting the breast cancer risk (p = 0.03).Conclusion: Factor analysis is useful for understanding which foods are consumed in combination and for studying the associations with biomarkers, while LCA is useful for classifying individuals into mutually exclusive subgroups and compares the disease risk between the groups.

Association of Egg Consumption, Metabolic Markers, and Risk of Cardiovascular Diseases

ObjectiveTo simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with CVD risk.MethodsTotally 4,778 participants (3,401 CVD cases subdivided into subtypes and 1,377 controls) aged 30-79 were selected from a nested case-control study based on the China Kadoorie Biobank. Targeted nuclear magnetic resonance was used to quantify 225 metabolites and derived traits in baseline plasma samples. Linear regression was conducted to assess associations between self-reported egg consumption and metabolic markers, which were further compared with associations between metabolic markers and CVD risk.ResultsEgg consumption was associated with 24 out of 225 markers, including positive associations for apolipoprotein A1, acetate, mean HDL diameter, and lipid profiles of very large and large HDL, and inverse associations for total cholesterol and cholesterol esters in small VLDL. Among these 24 markers, 14 of them were associated with CVD risk. In general, the associations of metabolic markers with egg consumption and of metabolic markers with CVD risk showed opposite patterns.ConclusionsIn the Chinese population, egg consumption is associated with several metabolic markers, which may partially explain the protective effect of egg consumption on CVD.

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 &lt; 0.01) while SZ patients in remission showed a significantly decreased APOA1 transcript variant 3 expression level and increased APOA4 mRNA expression level (p &lt; 0.01). mRNA expression levels of APOA1 transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (ptrend = 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.