ApoA1 Levels Research Articles

Associations of Serum Calcium, Magnesium Levels, and Their Ratio with Apolipoproteins in Chinese Adults with Coronary Artery Disease: a Cross-Sectional Study.

Former evidence regarding the associations of serum calcium (Ca) and magnesium (Mg) levels with apolipoproteins (Apos) in Chinese adults with coronary artery disease (CAD) were scarce. A total of 6781 patients with CAD were included in this cross-sectional study; mean age was 61.0years. The associations of serum Ca, Mg, and Ca/Mg ratio with Apos (e.g., ApoA1, ApoB, and ApoB/A1 ratio) were determined using multivariate analysis of covariance. Serum Ca, Mg, and Ca/Mg ratio tended to have positive associations with ApoA1, while negative associations of serum Ca, Mg, and Ca/Mg ratio with ApoB and ApoB/A1 ratio were detected. In multivariate analysis, serum Ca, Mg, and Ca/Mg ratio were positively associated with ApoA1 levels (Q [quintile] 5 vs. Q1: 1.245 vs. 1.151g/L for Ca, 1.207 vs. 1.188g/L for Mg, 1.202 vs. 1.171g/L for Ca/Mg ratio). In contrast, negative associations of serum Mg and Ca/Mg ratio with ApoB and ApoB/A1 ratio were shown. The corresponding ApoB and ApoB/A1 ratio values were 0.856 (vs. 0.887g/L) and 0.728 (vs. 0.771) for Mg, and 0.814 (vs. 0.854g/L) and 0.695 (vs. 0.751) for Ca/Mg ratio in Q5 compared with Q1. Serum Ca was inversely associated with ApoB and ApoB/A1 ratio (Q5 vs. Q4: 0.804 vs. 0.847g/L for ApoB; Q5 vs. Q1: 0.662 vs. 0.732 for ApoB/A1 ratio). Path analysis showed that mediating effects of BMI on the "Ca or Mg-Apos" associations were not found. In summary, serum Ca and Mg tended to have positive associations with ApoA1 levels in patients with CAD, but had inverse associations with ApoB levels and ApoB/A1 ratio. Serum Ca/Mg ratio may be a more precise marker than serum Mg or serum Ca measures alone in assessing Apos measures of CAD risk.

Association between Genetic Polymorphisms of MIR3142HG and the Risk of Steroid-Induced Osteonecrosis of the Femoral Head in the Population of Northern China

Background: Steroid-induced osteonecrosis of the femoral head (ONFH) is aseptic necrosis of the femoral head caused by glucocorticoid use. Once necrotic femoral head necrosis occurs, it irreversibly affects the quality of life seriously. Studies have shown that the susceptibility to steroid-induced ONFH is likely to be related to the variation of miRNA-coding genes. Therefore, this study aimed was to investigate the effect of MIR3142HG on steroid-induced ONFH. Methods: Agena MassARRAY was used to genotype MIR3142HG gene rs1582417, rs2431689, rs7727155, and rs17057846 in 199 patients and 725 healthy people. A genetic model and haplotype analysis were used to evaluate the relationship between the MIR3142HG polymorphism and the risk of steroid-induced ONFH. The odds ratio and 95% confidence intervals were obtained through logistic regression to assess the influence of gene polymorphisms on the occurrence of steroid-induced ONFH. Results: The consequences show that rs7727115 is a protective factor, it could reduce the risk of steroid-induced ONFH, and rs1582417 could increase the risk of steroid-induced ONFH. In the genetic model, rs1582417 was associated with increased risk of alcohol-induced ONFH in dominant model and log-additive model. rs7727115 showed a decreased risk in codominant model, dominant model, and log-additive model. In addition, rs2431689 is related to HDL-C (p = 0.012) and ApoA1 (p = 0.010) levels, and rs17057846 (p = 0.024) is related to ApoB levels. Thelinkage analysis indicated 3 single-nucleotide polymorphisms (rs2431689, rs7727115, and rs17057846) in MIR3142HG with significant chain imbalance. In addition, haplotype “GGG” of MIR3142HG was found out and is harmful for steroid-induced ONFH. Conclusion: Our results first confirm that the genetic polymorphism of MIR3142HG is associated with steroid-induced ONFH susceptibility in Chinese Han population.

Serum Vitamin D Levels and Risk Factors for Cardiovascular Complication in Diabetes

BACKGROUND: Diabetes is a significant contributor to dyslipidemia, which can contribute in cardiovascular complications. Vitamin D is crucial in preventing chronic metabolic diseases such as diabetes and heart disease (cardiovascular disease [CVD]). AIM: The objective of this study was to determine the relationship between Vitamin D levels and cardiovascular risk in type 2 diabetes mellitus. MATERIALS AND METHODS: This study is cross-sectional in nature. The study sampled 89 diabetic patients who met the study’s inclusion and exclusion criteria. After a 10 h fast, a venous blood test is performed to determine Vitamin D levels, apolipoprotein-A levels, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. The data are analyzed using SPSS. The Pearson correlation test (p > 0.05) was used to determine the connection. RESULT: Vitamin D levels were found to correlate with Apo-A1, TC, HDL-C, and triglyceride levels (p = 0.05), but not with LDL-C levels (p > 0.05). CONCLUSION: Vitamin D supplementation may assist DMT2 patients minimize their chance of developing CVD problems.

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.

Клініко-лабораторні та генетичні паралелі у хворих з гетеро- та гомозиготними сімейними гіперхолестеринеміями в Україні

The aim – clinical, laboratory and genetic parallels of patients with hetero- and homozygous familial hypercholesterolemia (FH) in Ukraine.Materials and methods. 231 FH patients were included in the Ukrainian FH Registry: 8 children (under 18 years of age) and 223 adult patients (197 heterozygous FH (HeFH) patients, 26 homozygous FH (HoFH) patients, verified according to DLCN criteria). The patients underwent general clinical, laboratory, instrumental examinations and genetic testing.Results and discussion. Among HeFH patients against the background of early manifestation of atherosclerosis, the male patients were more likely to have coronary heart disease and peripheral atherosclerosis, xanthomatosis and higher DLCN scores against an increase in % obesity and hypertension among HeFH women on the background of significantly lower DLCN. In the HoFH patients despite the inclusion of mostly reproductive aged females in the Registry, it is among women the most severe variants of FH were registered. They were characterized by a predominance of coronary heart disease, MI, xanthomatosis, the need for myocardial revascularization and prosthetic heart valves on the background of higher DLCN scores, cholesterol, LDL-C and ApoB values ​​up to 1.7±0.2 g/L and Lp (a) up to 119.5±31.4 nmol/L. In HoF patients and the most severe variants of the clinical course, who had levels of «statin naive» cholesterol and LDL above 20 mmol/L a more significant increase in these values were found: ApoB average 3.2±1.1 (maximum – 4.72) g/L and Lp (a) to 121.5±41.5 (maximum – 163) nmol/L and reduction of apoA1 level to 0.9±0.1 g/L.Conclusions. HeFH patients retain gender features of the risk factors profile, which corresponds to the main gender-related trends revealed by the Ukrainian population study with a predominance of coronary heart disease, peripheral atherosclerosis and xanthomatosis on the background of higher scores on DLCN in men. HoFH patients showed a reverse trend, namely among women – the predominance of coronary heart disease, myocardial infarction, xanthomatosis and the need for revascularization on the background of a higher score on DLCN. The cohort of HoFH women revealed the most severe FH cases with LDL-C &gt; 20 mmol/L, which was accompanied in 100 % of cases by early development of coronary heart disease and the need for myocardial revascularization, despite young age (36.5±3.9) and preserved reproductive function. According to HoFH patients genetic testing, pathogenetic mutations were detected in 72.3 % of women and 55.5 % of men (92.3 % in LDLR and 7.7 % in apoB). In the cohort of the most severe patients with LDL and LDL cholesterol &gt; 20 mmol/L, genetic mutations were detected in 100 %

Plasma Apolipoproteins A1/B and OxLDL Levels in Patients with Covid-19 As Possible Markers of the Disease.

The COVID-19 infection is associated with dyslipidemia and cardiovascular complications. The aim of the study was to determine the content of ApoA1, ApoB, and oxidized low-density lipoproteins (oxLDL) in the plasma of patients (n = 81) with COVID-19, diabetes, and cardiovascular disease (CVD). ApoA1, ApoB, and oxLDL were determined using enzyme-linked immunosorbent assay kits (Elabscience, United States). The measurements were performed at an optical wavelength of 450 nm. It was shown that the level of ApoA1 in the blood of patients with type 2 diabetes and especially with COVID-19 was significantly lower than in the blood of healthy people. Blood ApoA1 levels did not show a further decrease in patients with both COVID-19 and diabetes or CVD compared to patients with COVID-19 without concomitant diseases. It was found that the level of ApoB in the blood of patients with diabetes and, especially, with COVID-19 is significantly higher than in the blood of healthy people. Blood levels of ApoB and oxLDL are higher in patients with both COVID-19 and diabetes or CVD compared to patients with COVID-19 without comorbidities. Thus, levels of ApoA1, ApoB, and oxLDL may be promising markers of COVID-19.

A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia.

Objectives The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9-mAbs in the treatment of familial hypercholesterolemia (FH). Methods A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration's tool, and publication bias was evaluated by a contour-enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta-analysis was performed using R software, version 4.0.3. Results A meta-analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9-mAbs reduced the LDL-C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9-mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein-B (Apo-B), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and increased HDL-C and apolipoprotein-A1 (Apo-A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment.

Plasma Levels of Bile Acids Are Related to Cardiometabolic Risk Factors in Young Adults

ContextBile acids (BA) are known for their role in intestinal lipid absorption and can also play a role as signaling molecules to control energy metabolism. Prior evidence suggests that alterations in circulating BA levels and in the pool of circulating BA are linked to an increased risk of obesity and a higher incidence of type 2 diabetes in middle-aged adults.ObjectiveWe aimed to investigate the association between plasma levels of BA with cardiometabolic risk factors in a cohort of well-phenotyped, relatively healthy young adults.MethodsBody composition, brown adipose tissue, serum classical cardiometabolic risk factors, and a set of 8 plasma BA (including glyco-conjugated forms) in 136 young adults (age 22.1 ± 2.2 years, 67% women) were measured.ResultsPlasma levels of chenodeoxycholic acid (CDCA) and glycoursodeoxycholic acid (GUDCA) were higher in men than in women, although these differences disappeared after adjusting for body fat percentage. Furthermore, cholic acid (CA), CDCA, deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA) levels were positively, yet weakly associated, with lean body mass (LBM) levels, while GDCA and glycolithocholic acid (GLCA) levels were negatively associated with 18F-fluorodeoxyglucose uptake by brown adipose tissue. Interestingly, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), and GUDCA were positively associated with glucose and insulin serum levels, HOMA index, low-density lipoprotein cholesterol, tumor necrosis factor alpha, interleukin (IL)-2, and IL-8 levels, but negatively associated with high-density lipoprotein cholesterol, ApoA1, and adiponectin levels, yet these significant correlations partially disappeared after the inclusion of LBM as a confounder.ConclusionOur findings indicate that plasma levels of BA might be sex dependent and are associated with cardiometabolic and inflammatory risk factors in young and relatively healthy adults.

HDL subgroups and their paraoxonase‐1 activity in the obese, overweight and normal weight subjects

Obesity and overweight are significant public health problems because of higher risk for coronary artery disease (CAD). It is very important to determine new predictive markers to identify the CAD risk in obese and overweight. To aim this, we analysed HDL-C subgroups (HDL2-C and HDL3-C) and their paraoxonase-1 (PON-1) activity in obese, overweight and normal weight subjects. 71 obese, 40 overweight and 30 healthy subjects as a control group were enrolled the study. Serum lipids levels were determined with enzymatic colorimetric method. Further, PON-1 activities and HDL-C levels were determined by spectrophotometric methods. Non-HDL3-C concentrations were calculated with the subtraction of HDL3-C from total HDL-C. The mean serum levels of total HDL-C, HDL3-C, Non-HDL3-C and ApoA1 were higher in control group than obese and overweight groups. There were a statistically significant difference between obese and control group in terms of Lp(a), hsCRP and HOMA index. Higher total PON-1, non-HDL3 PON-1 and HDL3 PON-1 activities were found in the control group compared with obese and overweight groups. Total HDL was weakly negative correlated with the HOMA index, BMI and waist circumference. There was a weak negative correlation between non-HDL3-C and waist circumference. Altered HDL-subgroups pattern and decreased PON-1 activities may cause increased risk for CVD in obese and overweight individuals. Therefore determination of HDL subgroups and their PON-1 activity may improve risk prediction compared with measuring total HDL-C levels and its PON-1 activity alone. Body weight and insulin resistance appear to have a role in the decreased HDL-C levels and PON-1activity in obese. Further studies should be conducted to shed more light on impacts of these markers in CVD.

Metabolomics Profiling Discriminates Prostate Cancer From Benign Prostatic Hyperplasia Within the Prostate-Specific Antigen Gray Zone.

ObjectiveProstate cancer (PCa) is the second most common male malignancy globally. Prostate-specific antigen (PSA) is an important biomarker for PCa diagnosis. However, it is not accurate in the diagnostic gray zone of 4–10 ng/ml of PSA. In the current study, the performance of serum metabolomics profiling in discriminating PCa patients from benign prostatic hyperplasia (BPH) individuals with a PSA concentration in the range of 4–10 ng/ml was explored.MethodsA total of 220 individuals, including patients diagnosed with PCa and BPH within PSA levels in the range of 4–10 ng/ml and healthy controls, were enrolled in the study. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based non-targeted metabolomics method was utilized to characterize serum metabolic profiles of participants. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) methods were used for multivariate analysis. Receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic value of candidate metabolites in differentiating PCa from BPH. Correlation analysis was conducted to explore the relationship between serum metabolites and common clinically used fasting lipid profiles.ResultsSeveral differential metabolites were identified. The top enriched pathways in PCa subjects such as glycerophospholipid and glycerolipid metabolisms were associated with lipid metabolism. Lipids and lipid-like compounds were the predominant metabolites within the top 50 differential metabolites selected using fold-change threshold >1.5 or <2/3, variable importance in projection (VIP) > 1, and Student’s t-test threshold p < 0.05. Eighteen lipid or lipid-related metabolites were selected including 4-oxoretinol, anandamide, palmitic acid, glycerol 1-hexadecanoate, dl-dihydrosphingosine, 2-methoxy-6Z-hexadecenoic acid, 3-oxo-nonadecanoic acid, 2-hydroxy-nonadecanoic acid, N-palmitoyl glycine, 2-palmitoylglycerol, hexadecenal, d-erythro-sphingosine C-15, N-methyl arachidonoyl amine, 9-octadecenal, hexadecyl acetyl glycerol, 1-(9Z-pentadecenoyl)-2-eicosanoyl-glycero-3-phosphate, 3Z,6Z,9Z-octadecatriene, and glycidyl stearate. Selected metabolites effectively discriminated PCa from BPH when PSA levels were in the range of 4–10 ng/ml (area under the curve (AUC) > 0.80). Notably, the 18 identified metabolites were negatively corrected with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apo-B levels in PCa patients; and some were negatively correlated with high-density lipoprotein cholesterol (HDL-C) and Apo-A levels. However, the metabolites were not correlated with triglycerides (TG).ConclusionThe findings of the present study indicate that metabolic reprogramming, mainly lipid metabolism, is a key signature of PCa. The 18 lipid or lipid-associated metabolites identified in this study are potential diagnostic markers for differential diagnosis of PCa patients and BPH individuals within a PSA level in the gray zone of 4–10 ng/ml.

The fast progressor patient as an emerging clinical entity in patients with coronary atherosclerosis; exploratory study on possible molecular substrates

Abstract Background Once coronary atherosclerosis is clinically evident, it presents a very different rate of progression in each particular patient, being this progression one of the most important factors influencing on prognosis. Angiographic progression of lesions has been approached in some studies and certain driving factors have been identified. Nonetheless, clinical progression is more relevant but predictive factors remain less known. Purpose We aim to characterize a group of patients with accelerated clinical atherosclerosis (“fast progressors”, FP) and compare them to a stable group (“long standing stable”, LSS) both at baseline conditions, in order to explore potential markers or modulators that might have an impact on the prognosis. Methods We designed a case and control (1:2) study comparing the FP group (at least 3 different coronary revascularizations over the novo or previously non-significant lesions in a 10-year period of time), to a group of patients with LSS ischemic heart disease (those who have remained clinically stable during at least 10 years after a first coronary revascularization). We have analysed clinical, angiographic, social and environmental factors, as well as molecular substrates, the latter in baseline conditions. Results We identified 58 cases and compared them to 122 sex and age paired controls. Demographic characteristics and risk factors profile were similar in both groups. Clinical presentation at first event and coronary disease extent was also comparable in between groups. Figure 1 shows serum levels of patients during a stable phase of their disease. Creatinine was higher in the fast progressor group (FP) (p=0.03).Regarding the lipid profile LDLc and Apo B100 levels tended to be lower in the FP group most likely related to a more enhanced statin treatment in these group. Conversely, HDL and Apo A1 level were clearly lower in the FP group which could be explained due to an underlying higher risk condition. As to inflammatory determinants, CRP was found to be similar in both groups but IL-6 was significantly higher in the FP group. This could suggest that IL-6 levels might be a key marker of severity in the FP even at baseline condition. Of note, 10 patients showed IL-6 levels much higher than the mean. Moreover, we also assessed IL-6 genic expression, finding significant higher levels in the long standing stable group (LSS) (Figure 2). These findings suggest that the increase of IL-6 expression observed in the LSS group is not linked to a higher IL-6 production, therefore, the inflammatory state in those patients might be more controlled. Conclusion The main differential features at baseline of a clinically fast progressor patient compared to a long standing stable might reside in low HDL/Apo A1, along with a higher level of inflammation as estimated by IL-6 levels, but not CRP. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): AMGEN Serum levels of both groupsIL-6 levels

Intra-population differences of apolipoproteins in the aqueous humor

BackgroundEvidence suggests that proteins related to lipid metabolism, such as apolipoproteins, play an important role in the maintenance of normal vision. While several members of the apolipoprotein family are abundant in human aqueous humor (AH), their study remains difficult due to the AH’s small volume, low protein concentration, and the invasive nature of sample collection. In this study, we report the use of Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to discover associations between AH apolipoproteins and race, gender, and ocular structure in patients with and without primary open angle glaucoma (POAG).MethodsAH samples were collected from 231 patients undergoing phacoemulsification or glaucoma incisional surgery at the Medical College of Georgia, Augusta University and subsequently analyzed via LC-MS/MS. The number of peptide spectrum matches (PSMs) for each protein was used as a semi-quantitative measure of relative protein levels. Parameters related to ocular structure were determined using Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT). These data sets were probed for relationships between apolipoprotein levels and POAG, demographics (gender and race), and ocular structure.ResultsA total of ten apolipoproteins were detected in the 231 collected AH samples, with six detected in 100% of the samples, one detected in almost 57% of the samples and three detected in less than 10% of the samples. The levels of APOA1, APOC3, and APOD were higher among POAG subjects. Stratification by gender and race revealed demographic-specific variations. The levels of five apolipoproteins (APOA1, APOA2, APOA4, APOC3, and APOD) were higher in female POAG patients, whereas no apolipoprotein levels were altered in male POAG patients. The levels of APOA1, APOA2, APOA4, and APOD were increased in glaucomatous African American patients, whereas APOE and APOH levels were decreased in glaucomatous Caucasian patients. We also found distinct associations between apolipoprotein levels and OCT and HRT parameters in patients with and without POAG.ConclusionsThe intra-population variation in apolipoprotein levels highlights the heterogeneity of glaucoma as a disease, suggesting the importance of personalized treatments. Gender and race-specific alterations may be associated with higher risks of POAG in females and members of the African American population.

Effects of COVID-19 and diabetes mellitus on apolipoprotein A1 level in the blood plasma of patients

Background. Increased level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 (ApoA1) in plasma is associated with a reduced risk of developing cardiovascular diseases. In addition to its potential cardioprotective function, HDL and ApoA1, the main HDL apolipoprotein, also have antidiabetic properties. The aim of the study was to determine the level of ApoA1 in the blood of patients (n = 81) with diabetes mellitus and COVID-19. Materials and methods. ApoA1 was determined by enzyme-linked immunosorbent assay kits (Elabscience, USA). The measurements were performed at an optical density of 450 nm. Results. ApoA1 level in the blood of patients with diabetes and especially with COVID-19 was significantly lower than in healthy people. The study of the dependence of plasma ApoA1 content on the level of Hb1Ac, the gender and the type of diabetes showed that in blood of patients with type 2 diabetes the amount of ApoA1 is lower than in those with type 1 diabetes, and with an increase in the level of Hb1Ac the amount of ApoA1 decreases. There was also significant gender difference. With an increase in the body mass index, the content of ApoA1 in blood plasma decreases below normal — 0.9 g/L, and at body mass index &lt; 25 kg/m2, the amount of ApoA1 is significantly higher than the average lipoprotein level in diabetic patients. In individuals with newly diagnosed diabetes, the level of ApoA1 is significantly higher, and in patients with more than 10 years of illness, it is below average and below normal. Biguanide treatment, either in combination with other drugs (mainly insulin) or as monothe-rapy, does not significantly affect the level of ApoA1 compared to the entire group average. In patients treated with sulfonylurea, the level of ApoA1 is significantly lower than the average level for the group and the norm. A significant positive effect on the amount of ApoA1 in plasma was observed in people treated with a combination of drugs with sodium-glucose cotransporter type 2 inhibitors, insulin and especially dipeptidyl peptidase-4 inhibitors. However, insulin monotherapy did not significantly affect the ApoA1 content. Possible mechanisms of ApoA1 decrease in COVID-19 and diabetes are discussed. Conclusions. Thus, the level of ApoA1 may be one of the promising markers of severe COVID-19.

Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis

BackgroundPremorbid body mass index, physical activity, diabetes and cardiovascular disease have been associated with an altered risk of developing amyotrophic lateral sclerosis (ALS). There is evidence of shared genetic risk...

Apolipoprotein A1 level in plasma of patients with diabetes and diabetic patients with COVID-19 as a possible marker of disease

Increased levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) in plasma is associated with a reduced risk of developing cardiovascular diseases (CVD). In addition to its potential cardioprotective function, HDL and ApoA1, the main HDL apolipoprotein, also have antidiabetic properties. The aim of the study was to determine the level of ApoA1 in the blood of patients (n = 81) with type 2 diabetes mellitus and COVID-19. ApoA1 was determined by enzyme-linked immunosorbent assay (ELISA) (Elabscience, USA). The measurements were performed at an optical density of 450 nm. We showed that the level of ApoA1 in the blood of patients with type 2 diabetes and especially with COVID-19 was significantly lower than in the blood of healthy people. Blood ApoA1 levels did not show a further decrease in patients with both COVID-19 and diabetes compared with patients with COVID-19 without diabetes. Thus, the level of ApoA1 may be one of the promising markers of severe COVID-19.

Validation of serum apolipoprotein A1 in rabies virus-infected mice as a biomarker for the preclinical diagnosis of rabies.

Rabies is a type of acute fetal encephalitis caused by rabies virus (RABV). While it becomes incurable after symptom onset, it can be prevented by post‐exposure prophylaxis (PEP) during the long incubation period. While preclinical diagnosis aids the appropriate PEP administration, it is mostly nonfeasible owing to the absence of viremia or a specific antibody response during the incubation period. Here, an attempt was made to identify a serum biomarker for the preclinical diagnosis of rabies. Using the serum from a mouse inoculated intramuscularly (i.m.) with 5 × 105 focus‐forming units (FFU) of recombinant RABV expressing red firefly luciferase (1088/RFLuc) immediately before symptom onset, two‐dimensional differential gel electrophoresis was conducted, followed by mass spectrometry, and it was confirmed that apolipoprotein A1 (ApoA1) was up‐regulated. ELISA showed that the serum ApoA1 and specific antibody levels increased during the incubation period and on the day of symptom onset. Since a lower infectious dose can be used to induce the unstable and long incubation period generally observed in natural infection, the ApoA1 level in mice inoculated i.m. with 103 FFU of 1088/RFLuc was examined by monitoring viral dynamics using in vivo imaging. The serum ApoA1 and specific antibody levels were up‐regulated in 50% and 58.3% of mice exhibiting robust RABV replication, respectively, but not in mice exhibiting weak RABV replication. In addition, it was reported that ApoA1 was found to be a biomarker for neuronal damage. Additional biomarker candidates will be needed for the effective preclinical diagnosis of rabies.

High-density lipoprotein functionality in patients with hyperbaric oxygen therapy

High-density lipoprotein (HDL) cholesterol levels are associated with decreased risk of atherosclerotic disease, but also not all HDL are functionally equivalent. The functional status of HDL is closely linked to its primary protein component, apolipoprotein A-1 (ApoA-I) levels and paraoxonase 1 (PON1) enzyme. Functional changes of HDL may arise from hyperbaric oxygen therapy (HBO) induced posttranslational modification of ApoA-1 and PON1 levels. A total of 41 patients who met the research criteria were included in the study. On average, 30 sessions of HBO therapy were performed (range: 20-39). Laboratory measurements were performed at the beginning and at the end of HBO treatment in two groups of the same patients. We measured serum levels of Apo A-1, PON1, oxidized LDL (OxLDL) and routine lipid laboratory parameters to determine possible changes in HDL function with HBO therapy. As unexpected, long term HBO treatment have no effect on OxLDL and also on PON1 enzyme. However, the mean ApoA-1 values in the second group were statistically significantly increased than their pre-treatment values (P &lt; 0.003). This preliminary study showed that HBO therapy increased the amount of serum ApoA-1. Actually, it can be assumed that the treatment of HBO does not have a negative effect on HDL functionality. The increase in ApoA-1 with HBO therapy is probably aimed at protecting against oxidative stress in patients. As a result, there is a need for larger clinical trials to determine the possible effects of HBO therapy on HDL functionality.

Lipid and lipoprotein profile of patients with multiple myeloma before and after first-line treatment

Background and Aims: Low levels of high-density lipoprotein cholesterol (HDL-C) correlate with multiple myeloma (MM) patients while higher levels of APOA1 correlate with better survival. MM is an incurable hematological neoplasia, that is characterized by malignant plasma cells in bone marrow. Since existing data on the role of the lipoprotein transport system in MM development are very limited here we performed a detailed analysis of the structure and function of lipoproteins from MM patients before and after first-line treatment and in comparison to healthy donors.

Low serum level of apolipoprotein A1 may predict the severity of COVID-19: A retrospective study.

BackgroundDyslipidemia has been observed in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate blood lipid profiles in patients with COVID‐19 and to explore their predictive values for COVID‐19 severity.MethodsA total of 142 consecutive patients with COVID‐19 were included in this single‐center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID‐19 in comparison with 77 age‐ and gender‐matched healthy subjects, their predictive values for COVID‐19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves.ResultsThere were 125 and 17 cases in the non‐severe and severe groups, respectively. Total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non‐severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID‐19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800–0.935, p < 0.001), along with interleukin‐6 (IL‐6) (adjusted OR: 1.097, 95% CI: 1.034–1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834–0.941); moreover, the risk model established using ApoA1 and IL‐6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932–0.995).ConclusionBlood lipid profiles in patients with COVID‐19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID‐19.

High-density lipoprotein remodeling by phospholipid nanoparticles improves cholesterol efflux capacity and protects from atherosclerosis

The efficiency of cholesterol efflux from cells promoted by high-density lipoproteins (HDLs) depends on HDL concentration and functional properties. The term “dysfunctional HDL” describes HDLs with impaired protective properties. Cholesterol efflux capacity (CEC) of HDL is reduced in patients with atherosclerosis, but the exact mechanisms underlying this impairment are not well characterized. Enriching HDLs with phospholipids (PLs) improves CEC. Herein, we assessed the potential of PL nanoparticles in improving HDL functionality. We lipidated HDL subfractions by incubating with PL nanoparticles containing soybean polyunsaturated phosphatidylcholine. Incubating blood plasma with PL nanoparticles resulted in the dose-dependent lipidation of all HDL subfractions. Changes in apolipoprotein A1 (apoA-1) and PL concentrations were the most prominent in the HDL2 fraction. Concentrations of PL in the HDL3 fraction and the fraction with a density > 1.21 g/mL increased by 30–50%, whereas apoA-1 levels decreased. We hypothesized that PL nanoparticles may cause HDL remodeling that can improve their functions. The CECs of lipidated HDLs were analyzed by incubating apolipoprotein B (apoB)-depleted plasma with 3H-cholesterol-labeled THP-1 macrophages. The findings revealed a two-fold increase in cholesterol efflux compared with native apoB-depleted plasma. Moreover, intravenous administration of PL nanoparticles restored lipid profiles and effectively protected blood vessels from atherosclerosis progression in cholesterol-fed rabbits compared with that of fenofibrate and atorvastatin. PL nanoparticles also protected against atherosclerosis and decreased the atherogenic index. Altogether, these results indicate that PL nanoparticles can be used to correct the lipid composition and CEC of HDLs. Data AvailabilityAdditional data can be provided upon reasonable request from the date of publication of this article within 5 years. The request should be sent to the author-correspondent at the address cd95@mail.ru.