Serum apoB Research Articles

Glycated apolipoprotein B decreases after bariatric surgery in people with and without diabetes: A potential contribution to reduction in cardiovascular risk

Background and aimsThe causal relationship between LDL cholesterol (LDL-C) and the pathogenesis of atherosclerosis is well established. Previous studies have shown that modifications, glycation and oxidation of LDL enhance its atherogenic potential. Glycation of LDL occurs in it is main protein component, apolipoprotein B100 (ApoB). Our aim was to assess the effect of bariatric surgery on circulating glycApoB levels and understand the factors influencing changes in its circulating levels. MethodsWe measured glycApoB in 49 individuals before, 6 and 12 months after bariatric surgery. We also assessed clinical parameters, lipoproteins, markers of inflammation and glycaemia. Correlation analysis was done to understand associations between changes in variables from baseline to 12 months after surgery. ResultsReductions in glycApoB post-bariatric surgery were significant regardless of whether the patients suffered from type 2 diabetes (T2DM) or took lipid-lowering therapy. There were no significant differences in glycApoB levels at baseline and follow-up between participants with T2DM and those without. GlycApoB declined from baseline in non-diabetics at 6 months and significantly at 12 months (1.09 mg/l vs 0.63 mg/l vs 0.49 mg/l, p < 0.05), and in those with T2DM at 6 months and significantly at 12 months (1.77 mg/l vs 1.03 mg/l vs 0.68 mg/l, p < 0.05). The percentage change in glycApoB correlated (p < 0.05) with changes in glucose (ρ = 0.40), insulin (ρ = 0.41) and HOMA-IR (%) (ρ = 0.43). There were no significant associations between changes in glycApoB and changes in total serum ApoB, LDL-C, high sensitivity C-reactive protein, weight, or BMI. ConclusionsBariatric surgery reduces levels of glycApoB; this reduction is associated with decreased insulin resistance postoperatively. This potentially reflects the potent influence of obesity-related insulin resistance on lipoprotein glycation.Our observations are of potential importance in explaining the effectiveness of bariatric surgery in decreasing cardiovascular disease (CVD) risk in both T2DM and obese individuals without T2DM, as glycation of ApoB is known to be associated with increased atherogenesis.

Serum 25-hydroxyvitamin D3 is associated with homocysteine more than with apolipoprotein B.

The incidence of cardiovascular diseases (CVDs) has increased worldwide. Although a low serum vitamin D level is known to be associated with the risk of CVD, the mechanism is not well understood yet. The aim of this study was to determine the relationship of serum 25-hydroxyvitamin D3 (25[OH]D) with homocysteine and apolipoprotein B (ApoB). Of 777 subjects recruited from one health promotion center for routine heath exam from January 2010 to December 2016, 518 subjects were included in this study. Serum 25(OH)D, serum homocysteine, and other metabolic parameters including ApoB were analyzed. Simple and partial correlations were carried out after adjustments. Simple linear regression analysis was used for precise correlation of parameters. Multivariate regression analysis was done to know which factor (serum homocysteine or ApoB) was more related to serum 25(OH)D after adjustments. Finally, logarithms of homocysteine concentrations according to tertiles of serum 25(OH)D were compared. After sex and age adjustments, serum 25(OH)D showed negative correlations with serum homocysteine (r' = -0.114) and ApoB (r' = -0.098). In simple linear regression analysis, serum 25(OH)D showed a significant negative correlation with ApoB (P = 0.035). However, in multivariate regression analysis, serum 25(OH)D was significantly associated with serum homocysteine after adjustments (P = 0.022). In addition, serum homocysteine concentration was significantly high in the lowest 25(OH)D group (P = 0.046). Serum 25(OH)D concentration showed a stronger negative association with serum homocysteine than with ApoB.

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

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

Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

Using particulate matter (PM) mass as exposure metric does not reveal the intrinsic PM chemical characteristics or toxic potential, which is crucial for monitoring the sources of emission causing adverse health effects and developing risk mitigating strategies. Oxidative stress and ensuing lipid peroxidation (LPO) in the lung are crucial underlying mechanisms of action by which PM drives cardiorespiratory disease. In the current study, we have postulated and demonstrated that the intrinsic potential of PM to elicit LPO, defined as “LPO index” as a novel approach for characterizing oxidative potential of PM (PMOP) and predicting biological toxicity. First, we exposed unsaturated phosphatidylcholine (PC), an abundant phospholipid in the cell membrane, pulmonary surfactant, and lipoproteins to PM and analyzed the total burden of LPO byproducts generated as a measure of LPO index using a LPO reporter dye, BODIPY-C11. PM exposure resulted in a concentration-dependent increase in LPO. Second, we developed a novel method to expose the captured serum apoB100 lipoprotein particles to PM or its constituents and assessed the levels of specific oxidized-phospholipid on apoB100 particles by immunoassay using E06 monoclonal antibody (mab) that recognizes only PC containing oxidized-phospholipids (Ox-PCs). The immunoassay was highly sensitive to evaluate the PM LPO index and was modifiable by metal quenchers and exogenous antioxidant and radical quenchers. Third, to prove the pathophysiological relevance of Ox-PCs, we found that PM exposure generates Ox-PCs in mice lungs, pulmonary surfactant and lung cells. Fourth, we observed that treatment of macrophages with BAL fluid from PM exposed mice or PM-exposed pulmonary surfactant stimulated IL-6 production, which was abrogated by neutralization of Ox-PCs by mab E06 suggesting that Ox-PCs in lungs are proinflammatory. Overall, our study suggests that Ox-PCs as a probe of PM LPO index is a biologically relevant pathogenic biomarker and has a high value for evaluating PMOP.

The effects of genetic polymorphisms of APOE on circulating lipid levels in middle-aged and elderly chinese Fujian Han population: toward age- and sex-personalized management

BackgroundIncreased evidence has reported the association of genetic polymorphisms of Apolipoprotein E (APOE) with serum lipids. However, few studies have explored the combined effects of APOE, gender, and age.MethodsA total of 1,419 middle-aged and elderly subjects were randomly selected and studied. The APOE genotypes and the serum lipids were detected. The effects of APOE, gender, and age on serum lipids were preliminarily observed in general. The subjects were then divided into the middle-aged group (40–64 years old) and the elderly group (≥ 65 years old), for both males and females, to explore the combined effects of the APOE, gender, and age on serum lipids. Finally, a multivariate logistic regression model was used to evaluate the associations between the APOE allele carriers and the at-risk levels of dyslipidemia.ResultsThe serum TC, LDL-C, and ApoB in the ε2 carriers were lower than the ε3 carriers (all P < 0.05), and there was no significant difference in the ε4 carriers compared to the ε3 carriers in general (all P > 0.05). The serum LDL-C and ApoB of the ε2 carriers were lower than the noncarriers in the middle-aged and elderly males (all P < 0.05). The serum TC in the ε2 carriers was lower than the noncarriers only in middle-aged males (P < 0.05). As to the levels of serum HDL-C and ApoA1, the ε2 carriers were higher than the noncarriers in middle-aged females (all P < 0.05), and the ε4 carriers were lower than noncarriers in middle-aged males (P < 0.05). Especially, the serum TG in the ε4 carriers was significantly higher than the noncarriers in elderly females. The logistic regression analysis indicated that the ε2 carriers were less likely to have at-risk levels of high LDL-C in middle-aged and elderly males (all P < 0.05) versus low HDL-C in middle-aged females (P < 0.05). In contrast, the ε4 carriers were more likely to have at-risk levels of high TG in elderly females (P < 0.05).ConclusionsThe effects of the genetic polymorphisms of APOE on the serum lipids were both gender- and age-dependent in the middle-aged and elderly Chinese Fujian Han population.

Non-invasive skin cholesterol testing: a potential proxy for LDL-C and apoB serum measurements

BackgroundLipid management is the first line of treatment for decreasing the incidence of cardiovascular events in patients with coronary heart disease (CHD), and a variety of indicators are used to evaluate lipid management. This work analyses the differences in LDL-C and apoB for lipid management evaluation, as well as explores the feasibility of skin cholesterol as a marker that can be measured non-invasively for lipid management.MethodsThe prospective study enrolled 121 patients who had been diagnosed with acute coronary syndrome (ACS) at the department of emergency medicine of the First Affiliated Hospital of the USTC from May 2020 to January 2021, and the patients were grouped into Group I (n=53) and Group II (n=68) according to whether they had comorbid hyperlipidemia and/or diabetes mellitus. All patients were administered 10 mg/day of rosuvastatin and observed for 12 weeks. Lipid management was assessed on the basis of LDL-C and apoB, and linear correlation models were employed to assess the relationship between changes in these well accepted markers to that of changes in skin cholesterol.ResultsOut of 121 patients with ACS, 53 patients (43.80 %) had combined hyperlipidemia and/or diabetes mellitus (Group I), while 68 patients (56.20 %) did not (Group II). Cardiovascular events occur at earlier ages in patients with CHD who are comorbid for hyperlipidemia and/or diabetes (P<0.05). LDL-C attainment rate is lower than apoB attainment rate with rosuvastatin therapy (P<0.05), which is mainly attributable to patients with low initial LDL-C. Skin cholesterol reduction correlated with LDL-C reduction. (r=0.501, P<0.001) and apoB reduction (r=0.538, P<0.001). Skin cholesterol reduction continued over all time points measured.ConclusionsExamination of changes in apoB levels give patients with low initial LDL-C more informative data on lipid management than LDL-C readings. In addition, non-invasive skin cholesterol measurements may have the potential to be used independently for lipid management evaluation.

Association between apolipoprotein B and dietary fibers

Introduction Global awareness to the importance of natural fibers in vegetables and fruits are still generally very low. Indonesian people consume less fibers, which has been associated with the development of heart disease. Heart disease has been known as the leading cause of morbidity and mortality. Apolipoprotein B (ApoB) is a component of atherogenic particles that can be used as a marker for an increased risk of cardiovascular disease. Researches on apoB profile and its relationship with fiber intake has provided inconsistent results. This is an article review of the current literatures on the relationship between dietary fiber and serum apoB levels.&#x0D; Methods: This is an article review of the current literatures on the relationship between dietary fiber and apoB. We searched PubMed and Google Scholar using keyword “dietary fibers” and “ApoB” to capture meta-analyses, observational and experimental studies. A total of 97 publication and abstracts were screened for this review. After careful screening, nine studies were finally included.&#x0D; Results: Two studies did not find associations between dietary fiber and serum apoB, while other seven found the association. Dietary fiber has been reported to be involved in the metabolism of serum cholesterol and blood pressure; hence, the deficiency of dietary fiber intake is believed to contribute to the epidemic of cardiovascular diseases. Several factors including nutritional status, dietary diet pattern, age, gender, physical activity, and smoking habits might influence the relationship between dietary fiber and serum apoB.&#x0D; Conclusion: More studies are required in the future for better understanding on the effect of dietary fiber on the apoB; hence, the risk of cardiovascular diseases.

A randomized, placebo-controlled, double-blind study on the effects of SZL on patients with mild to moderate depressive disorder with comparison to fluoxetine

Ethnopharmacological relevanceKaixinsan (KXS) decoction, as an herbal formula, was used to treat the diseases, such as insomnia, amnesia, emotional disorders in ancient china. It has been demonstrated to be active in various animal models resembling human depression with multitarget effects. However, effective verification on the clinical application of KXS is still lacking. Supplements in this knowledge field are urgently needed. Aim of the studyThis very first study evaluated the efficacy and tolerability of ShenZhiLing (SZL) tablets (KXS preparation), compared with fluoxetine (FLX, positive comparator), in patients with mild to moderate depressive disorder. Materials and methodsIn this randomized, double-blind, parallel-group study, 156 patients with mild to moderate depression without taken any antidepressants in the past 6 months or 4 continuous weeks were randomized to receive either 3.2 g/d SZL plus 20 mg/d FLX placebo (SZL group) or 20 mg/d FLX plus 3.2 g/d SZL placebo (FLX group), for 8 weeks. Their clinical presentations and some metabolic indexes were assessed during the 8 weeks' visiting period. ResultsPatients in SZL group showed a statistically significant improvement after 8 weeks of treatment in HAM-D17 score (18.79±2.09 to 4.43±4.71, p<0.001) and self-rating depression scale (SDS) score (58.49±8.89 to 39.84±12.09, p<0.001), but not in N-back total respond time (1145.55±608.26 to 1128.47±387.49, p>0.05). In addition, no significant difference at 8 weeks of treatment was found between SZL and FLX groups in SDS score (39.84±12.09 vs. 36.63±12.44) and N-back respond time (1128.47±387.49 vs. 1089.43±352.08) as well as reduction of HAM-D17 score (14.79±4.88 vs. 15.24±4.29) (p>0.05 for all). However, the serum APOB, APOC3 and ALB levels and LDL-C/HDL-C ratio decreased significantly in patients after SZL treatment, while only APOB/APOA1 ratio decreased significantly in FLX group. Other metabolic indexes did not alter significantly after treated with SZL or FLX. ConclusionThe efficacy and safety profile of SZL are comparable to that of fluoxetine in patients with mild to moderate depression. The beneficial effect of SZL is probably associated with improvement of lipid metabolic balance.

Association of serum apolipoprotein B with retinal neurovascular structural alterations in patients with type 2 diabetes: an optical coherence tomography angiography study.

To investigate the association of serum apoB concentrations with retinal neurovascular structural alterations in type 2 diabetes patients without clinically visible retinopathy. Eyes with no clinically visible diabetic retinopathy (DR) from diabetic patients with or without dyslipidemia were included. Changes in retinal neural structures, including the ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (RNFL) thicknesses, and microvascular metrics, including macular vessel density (VD) and perfusion density (PD) of the superficial capillary plexus, were measured with optical coherence tomography angiography (OCTA). Correlations between inner retinal layer thickness and OCTA metrics were analyzed. The association of serum apoB and diabetic retinal neurovascular structures was identified with regression analysis. A total of 148 eyes in the diabetes group (n = 74) and dyslipidemia group (n = 74) were enrolled. GCL and RNFL thicknesses in patients in the dyslipidemia group were significantly thinner than those in the diabetes group (all p < 0.025). The total area of the VD and PD in the dyslipidemia group was also decreased compared to that of the diabetes group (p < 0.05) and was found to correlate with GCL and RNFL (all p < 0.01) thicknesses in all diabetic patients. Serum apoB levels were positively related to low-density lipoprotein (LDL) and total cholesterol (TC). Moreover, the average GCL thickness was significantly associated with serum apoB levels (all p < 0.05). GCL and RNFL thinning was significantly correlated with decreased retinal blood flow in diabetic patients with dyslipidemia. Strictly controlling serum lipids, especially apoB levels, might be an effective strategy for DR treatment.

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.

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.

Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction

BackgroundProprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG).MethodsThis prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions.ResultsSerum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05).ConclusionSerum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

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.

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.

Effects of lipid-lowering agents on plasma lipid profile and apolipoprotein B in patients with type 2 diabetes mellitus

Objectives: Type 2 Diabetes Mellitus (T2DM) accounts for about 90% of all cases of Diabetes Mellitus. Dyslipidaemia has been demonstrated to form a synergy with T2DM as risk factors for cardiovascular events. This study aimed to determine the plasma levels of Lipids and Apolipoprotein B-100 among Type 2 Diabetic patients, assess the effects of Lipid Lowering agents, and to study the relationship, if any, between these lipid parameters and glycemic control.Methods: One hundred and fifty participants consisting of fifty T2DM patients on a lipid-lowering agent, fifty newly diagnosed T2DM patients who are drug naïve (not on any anti-diabetic agent) and fifty apparently healthy non-diabetic controls were recruited for this study. Fasting blood samples were collected from all study participants for determination of Total Cholesterol (TC), LDL-C, Triglycerides(TG), High-Density Lipoprotein (HDL-C) and Apo B-100.&#x0D; Results: The results showed significant increases in plasma TC, LDL-C, TG and Apo B-100 with a remarkable reduction in plasma HDL-C level in the Type 2 Diabetic drug naïve group compared with the treatment and control groups. There was a significant positive correlation observed between serum Apo B-100 and level of glycaemia in the T2DM drug naïve group.Conclusion: This study further confirms the therapeutic benefits of lipid-lowering agents in reducing Apo B-100 among T2DM patients. Furthermore, maintaining good glycaemic control reduces the risk for the development of dyslipidaemia.&#x0D; Keywords: T2DM, Dyslipidaemia, Cardiovascular Diseases, Apolipoprotein B-100, Nigeria.

Measurement of apolipoprotein B levels helps in the identification of patients at risk for hypertriglyceridemic pancreatitis

BackgroundSevere hypertriglyceridemia (HTG) is a common cause of acute pancreatitis, although even moderate HTG may elevate this risk. Identifying patients who are prone to hypertriglyceridemic pancreatitis (HTGP) can facilitate early, preventative interventions. ObjectiveTo examine advanced lipoprotein profile (ALP) of hypertriglyceridemic patients with and without HTGP to identify lipid and lipoprotein parameters which may help improve risk stratification. MethodsThis was a retrospective cohort study of adult patients with serum triglycerides (TGs) ≥ 500 mg/dL who underwent ALP testing. Chart reviews were conducted to identify those who developed HTGP or not. Comparisons of lipid profiles of patients with and without HTGP were performed using chi-square or rank-sum tests. ROC curves were generated to identify lipid and lipoprotein parameters which helped improve prediction of HTGP beyond serum TG levels. ResultsFifty-eight subjects were included in the analysis. Twenty had at least one documented episode of HTGP. Among patients with HTGP, median serum TG concentrations were 2832 mg/dL vs. 978 mg/dL in the non-pancreatitis group (p < 0.001). Chylomicron TG/total TG, chylomicron TG/VLDL TG, chylomicron TG/apoB, total TG/total Cholesterol, and total TG/apoB were significantly higher among the pancreatitis group. Total serum TG/apoB had the best discriminant value for predicting HTGP with an AUC-ROC of 0.87 (p < 0.001). A cutoff of >10.6 was associated with a sensitivity of 90% and specificity of 75%. ConclusionMeasurement of serum apoB levels and calculation of serum TG/apoB ratio may help identify hypertriglyceridemic patients at risk for HTGP.

Sex-Specific Influence of the SCARB1 Rs5888 SNP on the Serum Lipid Response to Atorvastatin in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BackgroundEpidemiological studies have shown that there are sex differences in blood lipid levels and lipid responses to statins. Previous studies have shown that the rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in a sex-specific manner. The present study was undertaken to detect the sex-specific influence of the SCARB1 rs5888 SNP on the serum lipid response to atorvastatin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).MethodsA total of 158 unrelated ACS patients (108 males, 50 females) were enrolled, and all patients received atorvastatin 20 mg/daily after PCI. Genotyping of the rs5888 SNP was performed by polymerase chain reaction and direct sequencing. Serum lipid profiles were determined before treatment and after an average follow-up time of one year.ResultsThe baseline serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)AI levels were higher in females than in males (P<0.05). After treatment with atorvastatin, serum TC, LDL-C, and ApoB were decreased, and ApoAI was increased (P<0.05). The effects of atorvastatin on serum lipid levels were different between males and females, and females had greater decreases in TC, LDL-C and ApoB levels than males (P<0.05). The genotypic frequencies of the rs5888 SNP were not different between males and females. The atorvastatin response was not associated with the rs5888 SNP in males (P > 0.05). Nonetheless, in female individuals carrying the rs5888 T-allele, we observed a greater reduction in TC, LDL-C, and ApoB levels after the use of 20 mg/day atorvastatin (P<0.05).ConclusionThis study indicates that the SCARB1 rs5888 T-allele was associated with a greater reduction in serum TC, LDL-C, and ApoB after atorvastatin treatment in female patients with ACS undergoing PCI.

Association of serum Apolipoprotein B with cerebrospinal fluid biomarkers of Alzheimer’s pathology

ObjectiveTo examine whether apolipoprotein B (ApoB), apolipoprotein A‐1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in elderly adults with subjective cognitive decline (SCD).MethodsThis study included 507 objective cognitive normal participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database including 288 cognitive normal participants (CN) and 219 SCD. Multiple linear regression models were used to examine the associations of apolipoproteins with CSF AD biomarkers.ResultsCompared with control group, SCD participants with significant AD biological characteristics had lower ApoB levels (P = 0.0461). In total participants, lower level of serum ApoB was associated with decreases in CSF Aβ42 (P = 0.0015) and Aβ42/40 (P = 0.0081) as well as increases in CSF p‐tau/Aβ42 (P < 0.0001) and t‐tau/Aβ42 (P = 0.0013), independent of APOEɛ4 status. In further subgroup analysis, these associations were more significant in SCD participants (ApoB × Diagnose: P < 0.05). In addition, lower levels of ApoB were also found associated with increases in p‐tau in the SCD subgroup (P = 0.0263). Furthermore, these protective associations were more significant in the overweight participants (ApoB × weight: P < 0.05). Results showed no association between ApoA1 and CSF biomarkers.InterpretationThis study is the first to find protective associations of serum ApoB with CSF AD core biomarkers, especially in SCD individuals. It indicated that ApoB may be a potential biomarker for preclinical AD and may play different roles in different stages of AD.

Low Expression of APOB mRNA or Its Hypermethylation Predicts Favorable Overall Survival in Patients with Low-Grade Glioma.

BackgroundThis study was performed to explore the clinical and prognostic significance of APOB mRNA expression, DNA methylation and APOB mutation in patients with low-grade glioma (LGG).MethodsBioinformatic analysis was conducted using genomic, clinical and survival data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Serum APOB protein levels were measured via immunoturbidimetry in 150 patients with LGG and 100 healthy controls from Hubei General Hospital.ResultsThere was a negative association between the levels of APOB mRNA and DNA methylation (r=−0.355, P<0.0001) in patients with LGG from the TCGA database. Additionally, LGG patients with low levels of APOB mRNA exhibited better overall survival (OS) than those with high levels of APOB mRNA (HR=0.637, P=0.0085). The survival time of LGG patients with APOB hypermethylation was markedly longer than that of patients with APOB hypomethylation (HR=0.423, P=0.0185). The prognostic significance of APOB mRNA and DNA methylation was also validated with the CGGA cohort, and a similar conclusion was reached. APOB gene mutations were observed in 3% of patients with LGG from the TCGA database, and no association was detected between APOB mutations and OS (P=0.164). Furthermore, the levels of APOB protein were much lower in patients with LGG than in normal individuals (P=0.0022), and the expression of APOB protein was markedly different among groups when stratified by histological type (P<0.0001) and histological-molecular classification (P<0.0001).ConclusionAPOB mRNA expression is negatively regulated by DNA methylation in patients with LGG. Low expression or hypermethylation of APOB might predict relatively favorable survival in patients with LGG.

High ammonia exposure regulates lipid metabolism in the pig skeletal muscle via mTOR pathway

Ambient ammonia exposure has been known to perturb lipid metabolism in farm animals, but the underlying mechanism is unclear. The current study was conducted to investigate how ambient ammonia exposure influences lipid metabolism in the pig model. Twelve pigs were randomly divided into two groups, either exposed to 0 or 35 mg/m3 atmospheric ammonia for 25 days. Serum ammonia remained unchanged (p > 0.05), but increased serum urea concentration was found (p < 0.05) after ammonia exposure. Ammonia exposure also caused an increased C18:0, C18:2n6c, C18:3n6, C18:3n3, C20:0, C20:2, C20:3n6, C20:3n3, C22:0 concentrations and fat content in the longissimus dorsi muscle (p < 0.05), and also serum total triglyceride (p = 0.0294) and ApoB (p = 0.0061) contents. Analysis of serum free amino acids profile revealed that concentrations of ornithine, tyrosine, asparagine, histidine, phenylalanine, leucine, isoleucine, glutamine and valine were significantly increased in the pigs exposed to 35 mg/m3 ammonia (p < 0.05). RNA-Seq analysis showed that genes encoding enzymes involved in lipid synthesis (FASN, SCD and FADS1) and uptake (LDLR) were up-regulated, whereas genes related to lipolysis (PNPLA4, ANGPTL4 and CEL), transport (CPT1A, CPT1B and CPT2) and β-oxidation (ACADL, ACADVL, UCP2 and UCP3) were down-regulated. Furthermore, exposure to 35 mg/m3 atmospheric ammonia increased expression of mTOR (p = 0.0377) and its downstream P70S6K (p = 0.0139) and p-P70S6K (p = 0.0431), but decreased AMPK (p < 0.0001) and p-AMPK (p = 0.0071) in the longissimus dorsi muscle. In conclusion, high concentration of atmospheric ammonia exposure greatly interferes with amino acid metabolism, resulting in increased BCAAs and aromatic amino acids. The increased BCAAs production can up-regulate lipid synthesis and down-regulate β-oxidation by activating mTOR signaling and inhibiting AMPK signaling.