ApoA1 Levels Research Articles

The association between apolipoprotein A-1 plasma level and premature coronary artery disease: A systematic review and meta-analysis.

Apolipoprotein A-1 (Apo A-1) is a constituent of high-density lipoprotein (HDL) and emerging evidences put forward a potential association between Apo A-1 plasma levels and premature coronary artery disease (pCAD). The aim of the present study is to gather relative literature and perform a systematic review and meta-analysis regarding the association between serum ApoA-1 levels and pCAD. Medline (via PubMed), Scopus, Embase and Web of Science databases were searched from the inception of databases until December 7, 2020. All articles reporting the plasma levels of ApoA-1 in patients with pCAD and the control group were included. A meta-analysis with pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) was reported. Subgroup analyses were done based on the observed heterogeneity in results. Seventeen case-control studies were included. ApoA-1 plasma level was calculated to be lower in pCAD patients compared with the control group (SMD: -0.67; 95% CI: -0.48 to -0.86; P < .001). The subgroup analysis and meta-regression showed that the variation in gender distribution, the development level of the target population's country and quality score of included studies were the main sources of heterogeneity. It was observed that the relationship was only significant in the developed countries (P < .001). Also, the heterogeneity was reduced when the analysis was limited to males (I2 = 57.2%) and females only (I2 = 26.0%). In conclusion, there seems to be a significant association between the serum levels of ApoA-1 and pCAD. However, all of the included studies had a case-control design and since there is no good quality and prospective cohort studies included, reliability of the current evidence is debatable. Therefore, further well-designed cohort studies are required to assess the impact of serum ApoA-1 reduction on pCAD onset.

Genome-Wide Association Study Identifies a Functional SIDT2 Variant Associated With HDL-C (High-Density Lipoprotein Cholesterol) Levels and Premature Coronary Artery Disease.

Low HDL-C (high-density lipoprotein cholesterol) is the most frequent dyslipidemia in Mexicans, but few studies have examined the underlying genetic basis. Our purpose was to identify genetic variants associated with HDL-C levels and cardiovascular risk in the Mexican population. A genome-wide association studies for HDL-C levels in 2335 Mexicans, identified four loci associated with genome-wide significance: CETP, ABCA1, LIPC, and SIDT2. The SIDT2 missense Val636Ile variant was associated with HDL-C levels and was replicated in 3 independent cohorts (P=5.9×10−18 in the conjoint analysis). The SIDT2/Val636Ile variant is more frequent in Native American and derived populations than in other ethnic groups. This variant was also associated with increased ApoA1 and glycerophospholipid serum levels, decreased LDL-C (low-density lipoprotein cholesterol) and ApoB levels, and a lower risk of premature CAD. Because SIDT2 was previously identified as a protein involved in sterol transport, we tested whether the SIDT2/Ile636 protein affected this function using an in vitro site-directed mutagenesis approach. The SIDT2/Ile636 protein showed increased uptake of the cholesterol analog dehydroergosterol, suggesting this variant affects function. Finally, liver transcriptome data from humans and the Hybrid Mouse Diversity Panel are consistent with the involvement of SIDT2 in lipid and lipoprotein metabolism. This is the first genome-wide association study for HDL-C levels seeking associations with coronary artery disease in the Mexican population. Our findings provide new insight into the genetic architecture of HDL-C and highlight SIDT2 as a new player in cholesterol and lipoprotein metabolism in humans.

Effect of different exercises on effective factors involved in reverse cholesterol transfer in patients with coronary artery bypass surgery

Background: The present study aimed to compare the effect of different exercises on effective factors involved in reverse cholesterol transfer in patients with coronary artery bypass surgery (CABG). Materials and Methods: A number of 45 patients with CABGwere assigned to three groups: control (n=12), aerobic exercise (n=15), and resistance training (n=18). Three aerobic and resistance training sessions were performed per week for eight weeks. Anthropometric variables, expression of ABCG4 gen, as well as the serum levels of Apo-A and Apo-B, were measured before and after the training period. Data were analyzed using repeated measures of ANOVA. A p-value less than 0.05 was considered statistically significant. Results: Aerobic and resistance training significantly increased the expression of ABCG4 gene, compared to those in the control group (P=0.001); nonetheless, there was no significant difference between the two training groups (P= 0.021). Significant differences were observed in serum levels of Apo-A and Apo-B in both aerobic and resistance training groups, compared to those obtained in the control group (P=0.001). However, the difference between aerobic and resistance training groups was significant for Apo-A (P= 0.001), but not for Apo-B (P=1.000). Moreover, the ratio of Apo-A to Apo-B was significantly different for the resistance training group, compared to that in the control group (P= 0.001); nevertheless, it was not significant for the aerobic training group (P=1.000). Conclusion: As evidenced by the results of this study, resistance training improves cholesterol reverse transport regulators more than aerobic training; therefore, resistance training is recommended to regulate reverse cholesterol transfer.

Ellagic Acid Suppresses ApoB Secretion and Enhances ApoA-1 Secretion from Human Hepatoma Cells, HepG2.

The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.

Correlation of Long Non-coding RNA LncRNA-FA2H-2 With Inflammatory Markers in the Peripheral Blood of Patients With Coronary Heart Disease.

Objective: To characterize the expression of long non-coding RNA LncRNA-FA2H-2 in coronary heart disease (CHD) and its correlation with inflammatory markers.Methods: From December 2018 to December 2020, 316 patients at Henan Provincial People's Hospital who complained of chest tightness or chest pain and had coronary angiography to clarify their coronary artery conditions for definitive diagnoses were selected as the study subjects. Plasma was collected to detect white blood cells (WBCs), total cholesterol (TG), triglyceride cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and C-reactive protein (CRP) levels. Tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) levels were also measured using ELISA. The expression levels of lncRNA-FA2H-2 were measured using quantitative real-time PCR. The data obtained were analyzed by independent sample t-tests, rank sum tests, regression analyses, Pearson's or Spearman's correlation analyses, and receiver operating characteristic curves.Results: (1) Compared with the control group, the differences in age, sex, diabetes, smoking, drinking, body mass index (BMI), WBC, TC, and LDL-C in CHD were not statistically significant, while the differences in hypertension, TG, HDL-C, ApoA1, and CRP were statistically significant. (2) In the grouping of coronary lesion branches, patients with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TC, LDL-C, HDL-C, and ApoA1 differences were not statistically significant, but TG and CRP differences were statistically significant. (3) The relative expressions of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 were significantly upregulated in the CHD group (P < 0.001). (4) The results showed that the relative levels of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. In addition, positive correlations were found between the Gensini score and TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD patients. (5) LncRNA-FA2H-2 relative expression in the CHD group was significantly downregulated (P < 0.001). (6) The differences in the expression levels of LncRNA-FA2H-2 were statistically significant between the two comparative analyses (P < 0.01), except between the 2-branch lesion and 3-branch lesion groups. (7) LncRNA-FA2H-2 was not associated with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TG, TC, LDL-C, HDL-C, and ApoA1 (P > 0.05). (8) A correlation was found between LncRNA-FA2H-2 and MCP-1, and VCAM-1, ICAM-1, IL-6, and Gensini. (9) The results indicated that the relative levels of LncRNA-FA2H-2 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. A negative correlation was found between the Gensini score and LncRNA-FA2H-2. (10) ROC curve analyses of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD showed the area under the curve (AUC) = 0.832 (0.77, 0.893) with a cut-off value of 290.5, a sensitivity of 73%, and a specificity of 64%; AUC = 0.731 (0.653, 0.809) with a cut-off value of 396 and with a sensitivity of 59% and specificity of 79%; AUC = 0.822 (0.757, 0.887) with a cut-off value of 264 and with a sensitivity of 72% and specificity of 83%; AUC = 0.794 (0.715, 0.874) with a cut-off value of 201.5 and with a sensitivity of 75% and specificity of 65%; AUC = 0.760 (0.685, 0.834) with a cut-off value of 328 and with a sensitivity of 55% and specificity of 90%. (11) ROC curve analysis of LncRNA-FA2H-2 in CHD patients showed AUC = 0.834 (0.688, 0.85) with a cut-off value of 3.155 and with a sensitivity of 85% and specificity of 82%. (12) Logistic analyses showed that TNF-α, MCP-1, VCAM-1, IL-6, and LncRNA-FA2H-2 were independent risk factors for CHD.Conclusions: The expression of LncRNA-FA2H-2 was reduced and inversely correlated with inflammation-related factors in CHD patients. LncRNA-FA2H-2 may have potential as an inflammatory marker for risk assessment of CHD development.

Olanzapine leads to nonalcoholic fatty liver disease through the apolipoprotein A5 pathway

The antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In our study, at week 8, olanzapine treatment successfully induced hepatic steatosis in female C57 BL/6 J mice, which was independent of body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in HepG2 cells characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated with 8-week olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein levels in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis in vitro. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein levels and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA levels. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.

Association between cognitive impairment and apolipoprotein A1 or apolipoprotein B levels is regulated by apolipoprotein E variant rs429358 in patients with chronic schizophrenia.

ApoE gene polymorphism may be involved in the change in blood lipid profile and cognitive impairment of the general population. However, few studies explored the effects of ApoE gene polymorphism on blood lipid levels and cognition in schizophrenia. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was employed to evaluate the cognition and the SNPStats was used to investigate the association of ApoE rs429358 with schizophrenia. The models of analysis of covariance and multivariate analysis were conducted to investigate the effect of ApoE rs429358 on cognition in schizophrenia. Altogether, 637 patients with schizophrenia and 467 healthy controls were recruited in this study. The findings in the case group found that both the ApoA1 and ApoB levels were predictors for RBANS total score (p < 0.001 vs. p = 0.011), immediate memory (p < 0.001 vs. p = 0.019), language (p < 0.001 vs. p = 0.013), attention (p < 0.001 vs. p < 0.001), except ApoA1 level only was a predictor for visuospatial/constructional (p = 0.014) and delayed memory (p < 0.001). When the association was examined in different ApoE rs429358 genotype subgroups, the association between ApoA1 level and RBANS scores (except for the language score) or between ApoB level and RBANS scores (except for the attention score) was regulated by ApoE rs429358. Our results suggest that patients with schizophrenia have broad cognitive impairment compared with healthy controls. For patients with schizophrenia, both ApoA1 and ApoB levels were positively associated with cognition. There was a significant association between ApoA1 or ApoB levels and cognition in schizophrenia, which was regulated by the ApoE rs429358.

Association of lipoproteins and thyroid hormones with cognitive dysfunction in patients with systemic lupus erythematosus

BackgroundNeuropsychiatric manifestations occur in up to 75% of adult systemic lupus erythematosus (SLE) patients and are one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of neuropsychiatric SLE (NPSLE), which seriously affects the quality of life of patients. Dyslipidaemia and thyroid symptoms, which are prevalent in SLE patients, have both been related to neuropsychiatric disturbances, including significant psychiatric and cognitive disturbances. This study aimed to investigate whether cognitive dysfunction in patients with SLE was related to the expression of serum thyroid hormone and lipoprotein levels.MethodsA total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, and 81 SLE patients were divided into a high-cognition (n = 33) group and a low-cognition group (n = 48). The clinical and laboratory characteristics of the patients were compared; moreover, correlations between serum HDL-C, LDL-C, F-T3 and F-T4 levels and cognitive function were analysed. Serum levels of APOE, APOA1, IGF-1, and IGFBP7 in 81 patients were detected by ELISA, and the correlation between these four proteins and cognition was analysed separately.ResultsThe patients with SLE with abnormal cognitive function were less educated than the HCs. For low-cognition patients, the levels of albumin, F-T3 (P < 0.05) and F-T4 decreased, while D-dimer, anti-dsDNA antibody, and IgM levels increased. Serum F-T3 and F-T4 levels positively correlated with cognition. Furthermore, serum protein levels of APOE and APOA1 showed no difference between the high- and low-cognition groups. However, the serum APOE levels were negatively correlated with line orientation scores, and APOA1 levels were positively correlated with coding scores.ConclusionsSerum F-T3 and F-T4 levels were both positively correlated with four indexes of cognition (language was the exception), while serum APOE levels were negatively correlated with line orientation scores, APOA1 levels were positively correlated with coding scores, and IGFBP7 levels were negatively correlated with figure copy scores. These results demonstrated that F-T3 and F-T4 might be clinical biomarkers of cognitive dysfunction in SLE.

Gender characteristics of lipid profile parameters and markers of vascular inflammation in patients with stable angina pectoris in groups with presence and absence of type 2 diabetes.

The study of the parameters of the lipid profile and markers of the inflammatory reaction of the vascular wall in patients with stable angina pectoris in the presence or absence of type 2 diabetes mellitus (T2DM) is of great importance for revealing the gender characteristics of the pathophysiological mechanisms of the development and course of diseases, developing secondary prevention of complications and determining the prognosis. 194 patients with stable angina pectoris (SA), single-vessel coronary artery disease, mean age 60.3 ± 7.8 years were examined. Patients were divided into two groups: group 1 - patients with SA without diabetes 2 (n = 152), group 2 - with SA and diabetes 2 (n = 42). In each group, subgroups of men and women are distinguished. The study of biomarkers was carried out upon admission to the hospital on the background of therapy, taken on an outpatient basis. The study included a complex of parameters of the lipid spectrum, markers of the inflammatory response, endothelial dysfunction, and carbohydrate metabolism parameters. A comparative analysis of biomarkers revealed an excess of reference values of atherogenic lipid fractions in both groups of patients, regardless of patient gender. Moreover, in the first group of patients, in the subgroup of women, a significant excess of the level of TC, PL (a), and ApoA-1 was registered compared with the subgroup of men. In the second group, there were no significant differences in parameters between the male and female subgroups. Evaluation of the parameters of the inflammatory reaction revealed in the subgroup of women with T2DM a steady tendency to exceed the level of hs-CRP, TNF-α, homocysteine compared with both men and women in the SA group without T2DM. The logistic regression revealed the main biochemical markers that affect the aggravation of the course of IHD in women with T2DM: this is a uric acid level of more than 380 mmol / l - OS 11.5 (95% CI 1.71-77.69), TNF-α more 8 pg / ml - OR 7.5 (95% CI 1.07-52.46) and an increase in TG - OR 3.33 (95% CI 1.073-10.335). Thus, women of the 2nd group with the presence of T2DM are characterized by the highest level of atherogenic fractions of lipids, markers of vascular inflammation, glucose and HbA1c, which may indicate the greatest potential for the development of atherothrombotic complications in this subgroup of patients.

Clinical Characteristics of Lipid Metabolism in Untreated Patients with Anti-MDA5 Antibody-Positive.

ObjectiveClinical characterization of lipid metabolism in untreated patients with anti-melanoma differentiation-associated gene 5 antibodies-positive (anti-MDA5+).MethodsBody-mass index (BMI), autoantibodies, lipid levels, and serum ferritin levels in 57 anti-MDA5+ patients were determined in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University.ResultsPlasma high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) levels were significantly lower in deceased group than in the survival group (P < 0.05). Plasma levels of HDL and ApoA1 were significantly lower in patients who were simultaneously anti-MDA5+ and anti-Ro-52+ than in patients who were anti-MDA5+ alone (P < 0.05). Plasma levels of total cholesterol, low-density lipoprotein, HDL, and ApoA1 were significantly decreased in patients with high levels of serum ferritin compared with patients with low levels (P < 0.05). There were no significant differences in blood lipid levels between patients grouped according to BMI.Conclusion1) HDL and ApoA1 levels are important indicators of poor prognosis in anti-MDA5+ patients; 2) Dysregulated lipid metabolism in anti-MDA5+ patients is closely associated with anti-Ro-52 antibody and ferritin levels but independent of BMI; 3) HDL involvement in inflammation and immune regulation merits close attention by rheumatologists.

Associations of serum apolipoprotein A1, B levels and their ratio with blood pressure in Chinese adults with coronary artery disease.

We examined the relationships of apolipoprotein A1 (ApoA1), ApoB levels and ApoB/A1 ratio with blood pressure (BP) in Chinese adults with coronary artery disease (CAD). This cross-sectional study included 4921 adults with CAD. SBP, DBP, serum ApoA1 and ApoB levels were measured. The associations between Apo and BP were assessed by analyses of covariance. Serum ApoA1 was inversely associated with BP, whereas ApoB and the ApoB/A1 ratio exhibited positive associations with BP. For all subjects, a higher ApoA1 level was associated with lower SBP. Subjects in the fourth quartile for ApoA1 exhibited - 2.85 and - 2.63% lower DBP and mean arterial pressure (MAP), respectively than those in the third quartile. In contrast, higher ApoB and ApoB/A1 ratios were associated with higher SBP, DBP and MAP. The mean differences between ApoB quartiles 4 and 1 were 1.54% for SBP, 2.92% for DBP and 2.29% for MAP. The mean differences between the ApoB/A1 ratio quartiles 4 and 1 were 1.94% for SBP, 3.53% for DBP and 2.80% for MAP. In analyses stratified by gender, graded and inverse associations of ApoA1 with SBP, DBP and MAP were observed in both men and women, but positive associations were observed for ApoB and the ApoB/A1 ratio. Path analysis showed that BMI mediated the associations between ApoB and the ApoB/A1 ratio and SBP. In general, serum ApoA1 was inversely associated with BP in persons with CAD. In contrast, serum ApoB and the ApoB/A1 ratio were positively associated with BP, and these associations were mediated by BMI.

Association of altered lipid profile with disease activity, duration, and glucocorticoid treatment in patients with idiopathic inflammatory myopathies

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): AZV CR, Czech health research council MHCR, Ministry of Health Dzech republic Background Systemic inflammation, limited mobility, and glucocorticoid treatment in Idiopathic inflammatory myopathies (IIM) can have a negative impact on intermediate metabolic pathways, especially on lipid metabolism. Purpose The aim of this study was to assess the differences in the lipid profile of IIM patients and healthy controls (HC) and the association with disease-specific features. Methods 133 patients with IIM (106 females; mean age 60.3; disease duration 2.2 years; dermatomyositis, DM 47 / polymyositis, PM 41 / immune-mediated necrotizing myopathy, IMNM 45) and 133 age-/sex-matched HC (106 females, mean age 60.2) were included. Data are presented as median (IQR). Results Several differences in disease activity, the dose of glucocorticoids, prevalence of comorbidities, and serum lipid levels were observed among the three subtypes of IIM. Lipid profile parameters, especially levels of negative cardiovascular predictive markers such as TC, TG, LDL-C, Apo-B, and the atherogenic index were significantly higher compared to HC. The most significant changes were observed in IMNM compared to age-/sex-matched HC. Levels of TC, TG, LDL-C, apo-B, and non-HDL negatively correlated with disease duration but positively with laboratory markers of disease activity and the current prednisone equivalent dose. Higher levels of HDL-C were associated with decreased levels of CRP, which is in line with the negative correlation of apo-A levels with CRP, CK, and myoglobin. Conclusions: We have observed significant alterations in serum lipid parameters in our IIM patients compared to healthy age-/sex-matched individuals. Differences were also found among the three IIM subtypes. These alterations were associated with laboratory parameters of disease activity and the current dose of corticosteroids. Abstract Figure. Results - lipidogram in IIM and HC

Association of urinary ketamine and APOA1 levels with bladder dysfunction in ketamine abusers revealed via proteomics and targeted metabolite analyses

Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p < 0.0001) was detected via ELISA. Moreover, urinary ketamine, norketamine and dehydronorketamine contents (measured via LC-SRM-MS) were found to be positively correlated with overactive bladder syndrome score (OABSS) and APOA1 levels with urinary RBC, WBC, OABSS and numeric pain rating scale in KA. Collectively, our results may aid in developing new molecular tool(s) for management of ketamine-induced bladder dysfunction. Moreover, information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis.

Improvement of Total Flavonoids from Dracocephalum moldavica L. in Rats with Chronic Mountain Sickness through 1H-NMR Metabonomics

Background We analyzed the effects of total flavonoids from Dracocephalum moldavica L. (D. moldavica L.) on improving chronic mountain sickness (CMS) in rats using the NMR hydrogen spectrum (1H-NMR) metabonomics technology. Method We extracted the total flavonoids of D. moldavica L with 60% ethanol reflux. A CMS model was established with 48 Sprague–Dawley (SD) rats, which were then randomly divided into six groups (n = 8): control group (normal saline, 0.4 mL/100 g/d, ig); model group (normal saline, 0.4 mL/100 g/d, ig); nifedipine group (nifedipine tablets, 2.7 mg/kg/d, ig); and high-, middle-, and low-dose groups of total flavonoids from D. moldavica L. (DML.H, DML.M, and DML.L, receiving total flavonoids from D. moldavica L. at 400, 200, and 100 mg/kg/d, ig, respectively). The sera of the rats in all the groups were determined, and NMR hydrogen spectrum metabolomics was analyzed. The serum contents of apolipoproteins A1 (Apo-A1) and E (Apo-E) were determined, and histopathological changes in the brain tissue of each group were observed. Results Serum tests showed that total flavonoids from D. moldavica L. significantly increased the Apo-A1 and Apo-E levels in rats with CMS (P < 0.05). The results of serum metabonomics showed that total flavonoids from D. moldavica L can alleviate amino acid, energy, and lipid metabolism disorders in rats with CMS. Pathohistological examination of brain tissue showed that these flavonoids improved pathological changes, such as meningeal vasodilation, hyperemia, edema of brain parenchyma, inflammatory cell infiltration, increase in perivascular space, and increase in pyramidal cells. Conclusion Total flavonoids from D. moldavica L. have potential therapeutic effects on CMS. The possible mechanism is the reduction of oxidative damage through the alleviation of metabolism disorder.

Mechanism of Huo-Xue-Qu-Yu Formula in Treating Nonalcoholic Hepatic Steatosis by Regulating Lipid Metabolism and Oxidative Stress in Rats.

Huo-Xue-Qu-Yu formula (HXQYF) is a prescription consisting of Ginkgo biloba leaf and Paeonia lactiflora Pall. for treating hyperlipidemia and NAFLD in China. Here, we investigated the hepatic and renal function, oxidative stress and lipid metabolism, and potential mechanisms of HXQYF on nonalcoholic fatty liver disease (NAFLD) rat models. NAFLD rat models were induced with high-fat diet (HFD) and 10% fructose water for 18 weeks and orally administered with or without HXQYF simultaneously. The results showed that HXQYF (22.5, 45, 90 mg/kg) significantly improved blood lipid levels via reducing serum TC, TG, LDL-C, and APOB values and elevating HDL-C and APOA1 levels in NAFLD rats. The higher levels of ALT, AST, CR, and BUN in serum induced by HFD were reduced by HXQYF. HE staining showed that HXQYF (90 mg/kg) reduced the accumulation of fat droplets and alleviated inflammatory response in liver cells. Three doses of HXQYF exhibited notable antioxidant effects by elevating SOD, GSH, and CAT activities and decreasing MDA and OH-1 levels in the liver. Furthermore, abnormal lipid metabolism caused by HFD was alleviated by HXQYF, which was associated with the upregulation of PPAR-α, AdipoR2, and CPT1 mRNAs as well as the downregulation of CYP2E1 and SREBP-1c mRNAs in liver tissue. In conclusion, our work verified that HXQYF could reduce the degree of hepatic steatosis, suppress oxidative stress, and attenuate lipid metabolism, thus preventing NAFLD.

Serum APOA4 Pharmacodynamically Represents Administered Recombinant Human Hepatocyte Growth Factor (E3112).

Background: Hepatocyte growth factor (HGF) is an endogenously induced bioactive molecule that has strong anti-apoptotic and tissue repair activities. In this research, we identified APOA4 as a novel pharmacodynamic (PD) marker of the recombinant human HGF (rh-HGF), E3112. Methods: rh-HGF was administered to mice, and their livers were investigated for the PD marker. Candidates were identified from soluble proteins and validated by using human hepatocytes in vitro and an animal disease model in vivo, in which its c-Met dependency was also ensured. Results: Among the genes induced or highly enhanced after rh-HGF exposure in vivo, a soluble apolipoprotein, Apoa4, was found to be induced by rh-HGF in the murine liver. By using primary cultured human hepatocytes, the significant induction of human APOA4 was observed at the mRNA and protein levels, and it was inhibited in the presence of a c-Met inhibitor. Although mice constitutively expressed Apoa4 mRNA in the small intestine and the liver, the liver was the primary organ affected by administered rh-HGF to strongly induce APOA4 in a dose- and c-Met-dependent manner. Serum APOA4 levels were increased after rh-HGF administration, not only in normal mice but also in anti-Fas-induced murine acute liver failure (ALF), which confirmed the pharmacodynamic nature of APOA4. Conclusions: APOA4 was identified as a soluble PD marker of rh-HGF with c-Met dependency. It should be worthwhile to clinically validate its utility through clinical trials with healthy subjects and ALF patients.

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis.

The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels (P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores (P < 0.05), which were still significant after adjusting for confounding factors (P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA (P < 0.001). SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

Atherogenic Index of Plasma

Background: Cardiovascular diseases (CVDs) have become the leading cause of death among Indian population. It has been directly linked to hypercholesterolemia, particularly elevated plasma low-density lipoprotein-cholesterol (LDL-C) levels and low plasma high-density lipoprotein-cholesterol (HDL-C) levels. The lipid tetrad index (LTI) and lipid pentad index (LPI) have been recently described as a new form of assessment of lipid profiles. Hence, the present study was undertaken to evaluate the role of atherogenic index of plasma (AIP) and other lipid indices such as LTI and LPI in young myocardial infarction (MI) patients from North India. Methods: The present cross-sectional study was conducted in the Department of Biochemistry and Cardiology at GB Pant Institute of Postgraduate Medical Education and Research, New Delhi. A total of 240 individuals were included in the study in which 135 were patients of ST-elevation MI of the age 15–45 years, along with 105 age-matched controls during the period of July 2019 till December 2019. LTI was calculated as TC*TG*Lp(a)/HDL and LPI as TC*TG*Lp(a)*ApoB/ApoA1. AIP is calculated according to the formula: log (TG/HDL-C). Results: The lipid parameters including total cholesterol, triglyceride, LDL-C, and non-HDL-C were significantly increased in the acute MI cases in comparison to controls. HDL-C was significantly decreased in the cases. Lipoprotein (a), ApoB levels, and ApoB/ApoA1 were also significantly increased in the cases. On the other hand, ApoA1 levels were significantly decreased in the patients. LTI and LPI were significantly increased in the acute MI cases as compared to controls. On correlating lipid parameters with LTI and LPI, a significant positive correlation was observed with all lipid parameters – total cholesterol, triglyceride, LDL-C, Lp(a), and ApoB/ApoA1 except HDL-C which showed a negative correlation with LTI and a nonsignificantly negative correlation with LPI. HDL-C shows a significantly negative correlation with AIP in both cases and controls. Conclusions: This present study has evaluated Role of AIP along with lipid indices such as LTI &amp; LPI which helps in early identification of individuals with higher risk of premature CAD. AIP can be used as a better biomarker than other lipid indices in young MI patients, especially those associated with cardiovascular risk. At present, no Lp(a)-lowering drugs have been approved, hence early identification and intervention to modify risk factor may be helpful in prevention of development of MI in these patients with the help of LTI and LPI levels.

The Lipoprotein Transport System in the Pathogenesis of Multiple Myeloma: Advances and Challenges.

Multiple myeloma (MM) is an incurable neoplastic hematologic disorder characterized by malignant plasma cells, mainly in the bone marrow. MM is associated with multiple factors, such as lipid metabolism, obesity, and age-associated disease development. Although, the precise pathogenetic mechanisms remain unknown, abnormal lipid and lipoprotein levels have been reported in patients with MM. Interestingly, patients with higher APOA1 levels, the major apolipoprotein of high density lipoprotein (HDL), have better overall survival. The limited existing studies regarding serum lipoproteins in MM are inconclusive, and often contradictory. Nevertheless, it appears that deregulation of the lipoprotein transport system may facilitate the development of the disease. Here, we provide a critical review of the literature on the role of lipids and lipoproteins in MM pathophysiology. We also propose novel mechanisms, linking the development and progression of MM to the metabolism of blood lipoproteins. We anticipate that proteomic and lipidomic analyses of serum lipoproteins along with analyses of their functionality may improve our understanding and shed light on novel mechanistic aspects of MM pathophysiology.

Associations of Particulate Matter Sizes and Chemical Constituents with Blood Lipids: A Panel Study in Guangzhou, China.

Existing evidence is scarce concerning the various effects of different PM sizes and chemical constituents on blood lipids. A panel study that involved 88 healthy college students with five repeated measurements (440 blood samples in total) was performed. We measured mass concentrations of particulate matter with diameters ≤ 2.5 μm (PM2.5), ≤1.0 μm (PM1.0), and ≤0.5 μm (PM0.5) as well as number concentrations of particulate matter with diameters ≤ 0.2 μm (PN0.2) and ≤0.1 μm (PN0.1). We applied linear mixed-effect models to assess the associations between short-term exposure to different PM size fractions and PM2.5 constituents and seven lipid metrics. We found significant associations of greater concentrations of PM in different size fractions within 5 days before blood collection with lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A (ApoA1) levels, higher apolipoprotein B (ApoB) levels, and lower ApoA1/ApoB ratios. Among the PM2.5 constituents, we observed that higher concentrations of tin and lead were significantly associated with decreased HDL-C levels, and higher concentrations of nickel were associated with higher HDL-C levels. Our results suggest that short-term exposure to PM in different sizes was deleteriously associated with blood lipids. Some constituents, especially metals, might be the major contributors to the detrimental effects.