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INTRODUCTION AND OBJECTIVES Advanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. METHODS This cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. RESULTS The 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P

Aim Improving cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) has been regarded as a novel target for preventing cardiovascular disease. HDL reportedly has antioxidant properties which may contribute to its functions. We investigated changes in CEC with intake of the Japan Diet (JD) recommended by the Japan Atherosclerosis Society and the relationship of these changes to serum antioxidant concentrations. Methods A randomized parallel controlled clinical trial on JD intake was performed in Japanese patients with dyslipidemia. Ninety-eight participants were randomly divided into the JD (n=49) or the partial JD (PJD) (n=49) group. Nutrition education, based on each diet at baseline and at 3 months, was provided and the participants were followed up for 6 months. Results Mean CEC was 1.05 in total and correlated positively with HDL-cholesterol (p＜0.001) at baseline. CEC did not change while oxygen radical absorbance capacity (ORAC) was decreased in both groups (p＜0.001). Although serum total carotenoid increased in both groups, serum α-tocopherol decreased in the JD group as compared to the PJD group (p＜0.05). CEC correlated positively with HDL ORAC at baseline (p=0.021) and with serum total carotenoid at 3 and 6 months (p=0.005, 0.035). Changes in CEC correlated positively with changes in HDL ORAC at 3 months and serum total tocopherol at 3 and 6 months (p＜0.001). Conclusion CEC was not changed by JD education in Japanese patients with dyslipidemia who already had normal CEC at baseline. CEC was suggested to be positively associated with serum α- and γ-tocopherol and HDL ORAC.

Aims Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. We investigated similarities or differences between LDL-TG and sdLDL-C. Methods Fasting plasma was obtained from 1,085 patients with type 2 diabetes who were enrolled in the diabetes regional cohort study (ViNA Cohort). LDL-TG and sdLDL-C concentrations were measured using a homogeneous assay established by us. In a subset of subjects, LDL-TG and sdLDL-C levels were measured postprandially or after treatment with lipid-lowering drugs. Results In a quartile analysis, higher LDL-TG quartiles were associated with higher frequency of female and fibrate users, whereas sdLDL-C quartiles were associated with frequency of men, drinking, and metabolic syndrome-related measurements. Higher quartiles of LDL-TG/LDL-C were associated with smoking, drinking, fibrate users, and statin users. LDL-TG was significantly correlated with TG, LDL-C, sdLDL-C, and apolipoprotein (apo) B, with apoB being the primary determinant. LDL-TG correlated to high sensitive C-reactive protein (CRP) independently of other lipids. Mean LDL-TG did not change with fasting/non-fasting. Statin treatment reduced LDL-TG, whereas fibrates increased it, but these drugs reduced sdLDL-C equally. Conclusions LDL-TG levels were more tightly regulated by the number of LDL particles than plasma TG levels were. SdLDL-C was closely associated with metabolic syndrome-related factors, whereas LDL-TG was associated with low-grade systemic inflammation.

Introduction The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) index is a predictive factor for atherosclerosis, which is associated with oxidative modifications. Objective To assess the association of the index with oxidative stress markers. Methods 444 subjects were included and were clinically, anthropometrically and biochemically characterized; superoxide dismutase, glutathione peroxidase 3 (GPx3), magnesium and oxidized LDL (oxLDL) index (oxLDL/HDL) were quantified. Results A decrease of 1.014 units in the LDL/HDL index was associated with a superoxide dismutase increase of 1 unit/mL (p = 0.030), while a decrease of 0.023 units was associated with a GPx3 increase of 1 nmol/min/mL (p < 0.0005). An increase of one unit in the index was associated with an increase of 0.831 in the oxLDL/HDL index (p < 0.05). After controlling for the effect of gender, age, smoking, obesity and insulin resistance, a reduction of 0.001 per index unit was associated with an increase of 1 µg/g of magnesium in the nails (p = 0.020). Conclusions The LDL/HDL index shows an inverse relationship with the antioxidant status and a direct relationship with oxidation status, regardless of other cardiovascular and oxidative stress risk factors.

Purpose We hypothesized that the effect of blood lipid–related metabolites on primary open-angle glaucoma (POAG) would differ according to specific lipoprotein particles and lipid sub-fractions. We investigated the associations of blood levels of lipoprotein particles and lipid sub-fractions with POAG. Design Cross-sectional study. Participants Individuals recruited for the baseline visit of the population-based Singapore Epidemiology of Eye Disease study (n = 8503). Methods All participants underwent detailed standardized ocular and systemic examinations. A total of 130 blood lipid–related metabolites were quantified using a nuclear magnetic resonance metabolomics platform. The analyses were conducted in 2 stages. First, we investigated whether and which lipid-related metabolites were directly associated with POAG using regression analyses followed by Bayesian network modeling. Second, we investigated if any causal relationship exists between the identified lipid-related metabolites, if any, and POAG using 2-sample Mendelian randomization (MR) analysis. We performed genome-wide association studies (GWAS) on high-density lipoprotein (HDL) 3 cholesterol (after inverse normal transformation) and used the top variants associated with HLD3 cholesterol as instrumental variables (IVs) in the MR analysis. Main Outcome Measure Primary open-angle glaucoma. Results Of the participants, 175 (2.1%) had POAG. First, a logistic regression model showed that total HDL3 cholesterol (negatively) and phospholipids in very large HDL (positively) were associated with POAG. Further analyses using a Bayesian network analysis showed that only total HDL3 cholesterol was directly associated with POAG (odds ratio [OR], 0.72 per 1 standard deviation increase in HDL3 cholesterol; 95% confidence interval [CI], 0.61–0.84), independently of age, gender, intraocular pressure (IOP), body mass index (BMI), education level, systolic blood pressure, axial length, and statin medication. Using 5 IVs identified from the GWAS and with the inverse variance weighted MR method, we found that higher levels of HDL3 cholesterol were associated with a decreased odds of POAG (OR, 0.91; 95% CI, 0.84–0.99, P = 0.021). Other MR methods, including weighted median, mode-based estimator, and contamination mixture methods, derived consistent OR estimates. None of the routine lipids (blood total, HDL, or low-density lipoprotein [LDL] cholesterol) were associated with POAG. Conclusions Overall, these results suggest that the relationship between HDL3 cholesterol and POAG might be causal and specific, and that dysregulation of cholesterol transport may play a role in the pathogenesis of POAG.

Aqueous and hydroethanoic extracts prepared from leaves of Aloysia triphylla (L'Her.) Britton (lemon verbena) and Trigonella foenum-graecum L. (fenugreek) seeds were evaluated for in vivo hypocholesterolemic and anti-inflammatory effects. The results of administration of A.triphylla leaf and T. foenum-graecum extracts on serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low density lipoprotein (VLDL) in hypocholesterolemic mice were evaluated. Mice groups treated with both aqueous and hydroethanoic extracts of A. triphylla showed reduced total cholesterol (161.60 and 162.60 mg/dl, for mice groups treated with respective extracts) and LDL (79.16 and 99.04 mg/dl, for mice groups treated with respective extracts) levels as compared to the hypercholesterolemic group (253.00 and 160.00 mg/dl for TC and LDL, respectively). A similar trend was observed with the aqueous and hydroethanoic extracts of T. foenum-groecum seeds. Mice treated with hydroethanoic extracts (200 mg/kg body weight) of A. triphylla leaves and T. foenum-groecum seeds showed significantly reduced triglyceride and VLDL levels compared to the group treated with atorvastatin (18.76 and 18.20 mg/dl, respectively). In terms of phytochemical composition, caffeic acid were detected in both A. triphylla leaves and T. foenum-graecum seeds extracts. However, rutin and luteolin have not been detected in any extracts of A. triphylla and T. foenum-graecum. Data collected from this study support the fact of future development of novel botanical remedies from A. triphylla leaves and T. foenum-graecum seeds for managing hypercholesterolemia and atherosclerosis.

Chronic kidney disease (CKD) is accompanied with extensive cardiovascular calcification, in part correlating with functional vitamin K deficiency. Here, we sought to determine causes for vitamin K deficiency beyond reduced dietary intake. Initially, vitamin K uptake and distribution into circulating lipoproteins after a single administration of vitamin K1 plus K2 (menaquinone 4 and menaquinone 7, respectively) was determined in patients on dialysis therapy and healthy individuals. The patients incorporated very little menaquinone 7 but more menaquinone 4 into high density lipoprotein (HDL) and low-density lipoprotein particles than did healthy individuals. In contrast to healthy persons, HDL particles from the patients could not be spiked with menaquinone 7 in vitro and HDL uptake was diminished in osteoblasts. A reduced carboxylation activity (low vitamin K activity) of uremic HDL particles spiked with menaquinone 7 vs. that of controls was confirmed in a bioassay using human primary vascular smooth muscle cells. Kidney menaquinone 4 tissue levels were reduced in 5/6-nephrectomized versus sham-operated C57BL/6 mice after four weeks of a vitamin K rich diet. From the analyzed enzymes involved in vitamin K metabolism, kidney HMG-CoA reductase protein was reduced in both rats and patients with CKD. In a trial on the efficacy and safety of atorvastatin in 1051 patients with type 2 diabetes receiving dialysis therapy, no pronounced vitamin K deficiency was noted. However, the highest levels of PIVKA-II (biomarker of subclinical vitamin K deficiency) were noted when a statin was combined with a proton pump inhibitor. Thus, profound disturbances in lipoprotein mediated vitamin K transport and metabolism in uremia suggest that menaquinone 7 supplementation to patients on dialysis therapy has reduced efficacy.

OBJECTIVES Studies suggest an association between elevated total serum cholesterol (TC), particularly low-density lipoprotein (LDL), and osteoarthritis (OA). We evaluated the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA. METHODS We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee x-rays and MRIs were obtained and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of: cartilage loss and synovitis on MRI and of knee pain using the WOMAC scale. We carried out logistic regression adjusting for age, sex, BMI, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures and did sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL or low HDL increased risk. RESULTS We studied 337 cases with incident symptomatic OA and 283 cases with incident radiographic OA. Mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis or worsening knee pain. CONCLUSION Our data do not support an association between total cholesterol, LDL or HDL with OA outcomes.

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 < 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.

Purpose Erectile dysfunction (ED) has increased prevalence by age and significantly affects the quality of life of men and their partners. To investigate the relationship between ED and red blood cell distribution width (RDW) values. Materials and method Between September 2019 and December 2019, a total of 192 individuals comprising those that were admitted to the urology outpatient clinic with ED complaints and healthy volunteers from among hospital staff were prospectively included in the study. The participants were divided into two groups according to the international erectile function index (IIEF-5) as ED group (n = 148) and control group (n = 44). Results There was no statistically significant difference between the two groups in terms of age, smoking status, presence of hypertension, triglyceride, low-density lipoprotein, high-density lipoprotein, total cholesterol, total prostate-specific antigen and haematocrit values. Body mass index, fasting blood sugar, neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR) were significantly higher in the ED group (28.5 ± 27.4 kg/m2 vs 26.8 ± 26.5 kg/m2, p = .021, 109.05 ± 49.7 mg/dl vs 93.39 ± 10.2 mg/dl, p Conclusion Based on the strong relationship between RDW and ED, we consider that RDW may be a new indicator in the diagnosis of ED.

Background Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. Objectives This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. Methods After 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. Results Retention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. Conclusions A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.

Late-stage dry age-related macular degeneration (AMD) or geographic atrophy (GA) is an irreversible blinding condition characterized by degeneration of retinal pigment epithelium (RPE) and the associated photoreceptors. Clinical and genetic evidence supports a role for dysfunctional lipid processing and accumulation of harmful oxidized lipids in the pathogenesis of GA. Using an oxidized low-density lipoprotein (ox-LDL)-induced RPE death assay, we screened and identified sterically-hindered phenol compounds with potent protective activities for RPE. The phenol-containing PPARγ agonist, troglitazone, protected against ox-LDL–induced RPE cell death, whereas other more potent PPARγ agonists did not protect RPE cells. Knockdown of PPARγ did not affect the protective activity of troglitazone in RPE, confirming the protective function is not due to the thiazolidine (TZD) group of troglitazone. Prototypical hindered phenol trolox and its analogs potently protected against ox-LDL–induced RPE cell death whereas potent antioxidants without the phenol group failed to protect RPE. Hindered phenols preserved lysosomal integrity against ox-LDL–induced damage and FITC-labeled trolox was localized to the lysosomes in RPE cells. Analogs of trolox inhibited reactive oxygen species (ROS) formation induced by ox-LDL uptake in a dose-dependent fashion and were effective at sub-micromolar concentrations. Treatment with trolox analog 2,2,5,7,8-pentamethyl-6-chromanol (PMC) significantly induced the expression of the lysosomal protein NPC-1 and reduced intracellular cholesterol level upon ox-LDL uptake. Our data indicate that the lysosomal-localized hindered phenols are uniquely potent in protecting the RPE against the toxic effects of ox-LDL, and may represent a novel pharmacotherapy to preserve the vision in patients with GA.

Lipid-driven cardiovascular disease (CVD) risk is caused by atherogenic apolipoprotein B (apoB) particles containing low-density lipoprotein cholesterol (LDL-C), triglycerides and lipoprotein(a) [Lp(a)] and resembles a large and modifiable proportion of the total CVD risk. While a surplus of novel lipid-lowering therapies has been developed in recent years, management of lipid-driven CVD risk in the Netherlands remains suboptimal. To lower LDL‑C levels, statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibiting antibodies are the current standard of therapy. With the approval of bempedoic acid and the silencing RNA inclisiran, therapeutic options are expanding continuously. Although the use of triglyceride-lowering therapies remains a matter of debate, post hoc analyses consistently show a benefit in subsets of patients with high triglyceride or low high-density lipoprotein cholesterol levels. Pemafibrate and novel apoC-III could be efficacious options when approved for clinical use. Lp(a)-lowering therapies such as pelacarsen are under clinical investigation, offering a potent Lp(a)-lowering effect. If proven effective in reducing cardiovascular endpoints, Lp(a) lowering holds promise to be the third axis of effective lipid-lowering therapies. Using these three components of lipid-lowering treatment, the contribution of apoB-containing lipid particles to the CVD risk may be fully eradicated in the next decade.

Aims: Lipoprotein (a) deposition in coronary vascular plaques and cerebral vessels is a recognized risk factor for cardiovascular disease, and research supports its role as a “repair factor” in vascular walls weakened by vitamin C deficiency. Background: Humans depend on dietary vitamin C as an important antioxidant and as a cofactor in collagen synthesis, yet are prone to vitamin C deficiency. The brain is the one with the highest vitamin C content, owing to its high oxygen consumption and oxidative stress. It has been shown that brain aging is accompanied by accumulated oxidative damage, which can lead to memory decline and neurological diseases. Objective: Our transgenic mouse, Gulo (-/-); Lp(a)+, presents a unique model for the study of key aspects of human metabolism with respect to a lack of internal vitamin C synthesis and the production of human lipoprotein(a). Methods: This mouse model was used in our study to investigate the effects of prolonged intake of low and high levels of vitamin C, at different ages, on oxidative damage, cholesterol levels and lipoprotein( a) deposition in the brain. Result: The results show that a long-term high vitamin C intake is important in maintaining brain cholesterol homeostasis and preventing oxidative damage in Gulo(-/-);Lp(a)+ mice as they age. Moreover, we observed that the formation of brain lipoprotein(a) deposits was negatively correlated with brain level of vitamin C, thereby confirming its role as a stability factor for an impaired extracellular matrix. Conclusion: Our study emphasizes the critical role of vitamin C in protecting brain health as we age. Other: Our findings show that optimal vitamin C intake from early life to old age is important for brain health as it prevents oxidative stress damage and maintains cholesterol homeostasis in the brain. More importantly, the negative correlation between brain ascorbic levels and the formation of Lp(a) deposit on the choroid plexus further emphasizes the critical role of vitamin C in protecting brain health throughout the normal aging process.

Background The liver plays a key role in regulating whole body cholesterol homeostasis. Hepatic cholesterol accumulation causes liver injury in fatty liver disease and hypercholesterolemia increases the risk of cardiovascular disease. MicroRNAs (miRNAs, miRs) have been shown to regulate various pathways in cholesterol metabolism. Recently, miR-185 has been shown to regulate sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR) to modulate cholesterol synthesis and uptake. Materials and methods The role of miR-185 in regulating diet-induced metabolic disorders were studied in liver-specific miRNA-185 knockout (L-miR-185 KO) mice. Results L-miR-185 KO mice developed worsened hepatic steatosis upon high fat high cholesterol Western diet feeding with accumulation of triglyceride and cholesterol in the liver. In addition, L-miR-185 KO mice developed hypercholesterolemia upon Western diet feeding. Gene expression analysis showed that L-miR-185 KO mice did not show increased hepatic mRNA expression of SREBP2 or its targets LDLR and HMG-CoA reductase (HMGCR). Although expression of miR-185 mimic inhibited the mRNA of SREBP2, HMGCR and LDLR in HepG2 cells, miR-185 inhibitor did not increase the mRNA of SREBP2, HMGCR or LDLR in HepG2 cells. Conclusions In conclusion, we reported that L-miR-185 KO mice were more sensitive to Western diet induced hepatic steatosis and hypercholesterolemia. The molecular mechanisms underlying these metabolic changes remain to be investigated in future studies.

Rotigotine is a non-ergoline dopamine agonist that has been licensed for the treatment of Parkinson’s disease. Cardiovascular diseases are the world’s leading cause of death. Ox-LDL- induced endothelial damages are involved in the initiation and progression of cardiovascular diseases. In this study, we assessed the beneficial properties of Rotigotine on ox-LDL-induced insults to HUVECs to highlight its potential use in the treatment of cardiovascular diseases. Our findings show that Rotigotine suppresses the expressions of low-density lipoprotein receptor (LDL-R), proprotein convertase subtilisin/kexin type 9 (PCSK-9), and sterol regulatory element-binding protein (SREBP-2). It also inhibits ox-LDL-induced cholesterol accumulation in endothelial cells (ECs), improves U937 monocytes adhesion, and decreases the representation of NADPH oxidase (NOX-4) and generation of reactive oxygen species (ROS) in endothelial cells (ECs). Furthermore, Rotigotine inhibited the expressions of both vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs and had anti-inflammatory efficacy in ox-LDL-induced cells by inhibiting the expressions of pro-inflammatory cytokines. Notably, Rotigotine inhibits the activation of nuclear factor-kappaB (NF-κB) by preventing nuclear translocation of NF-κB p65 and reducing the luciferase activity of NF-κB reporter. We, therefore, conclude that these effects of Rotigotine on HUVECs suggest that it may play a therapeutic role in cardiovascular diseases.

This work aims to establish a quality control method and evaluate the effects in glucose and lipids for fruit body of Isaria cicadae Miquel from strain Ic-17-7(Ic-17-7fb) in type 2 diabetes (T2DM) rat model. Random amplified polymorphic DNA, sequence-characterized amplified region, and high-performance liquid chromatography (HPLC) were used for the quality control of Ic-17-7fb. The pharmacological effects on streptozocin (STZ)-induced high-fat diet-fed Albino Wistar rats, divided into model, metformin, fruiting body of Ic-17-7fb (0.166 g/kg and 0.5 g/kg) and control group were evaluated. The fasting blood glucose (FBG), blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-c), and low-density lipoprotein (LDL-c) were measured. The Ic-17-7fb could amplified a single specific band by S11-2-F3 and S11-2-R3 primers to validate. An HPLC-based quality and quantity was established and used for industrial application. The content of adenosine and N6-(2-hydroxyethyl) adenosine (HEA) of the cultivated Ic-17-7fb were analyzed. All of the validation lots of cultured Ic-17-7fb passed the quantity control of the training set (0.90 mg/g of adenosine and 0.89 mg/g of HEA). The average FBG in the 2ed -week were 4.89 ± 0.42 (control), 26.10 ± 5.77 (model), 23.63 ± 6.15 (metformin), 17.96 ± 9.36 (Ic-17-7fb for 0.166 g/kg), and 19.69 ± 8.71 mmol/L (Ic-17-7fb for 0.5 g/kg). The fruit body of Ic-17-7 (0.166 g/kg) treatment significantly was reduced by 31.19% compared with the model in the 2ed-week (p < 0.01). Ic-17-7fb (0.166 g/kg) significantly decreased the fasting blood glucose after 2 weeks of administration. Metformin, Ic-17-7fb (0.166 g/kg), and Ic-17-7fb (0.5 g/kg) reduced the TC, TG, HDL-c, and LDL-c compared with the T2DM model treatment at the 6th week of treatment (p < 0.05). This study established the first quality standard for Ic-17-7fb and has an effective application in the treatment of T2DM. The reliable method and pharmacological effect can be generalized to a broader population and possibility study for future research.

BACKGROUND/OBJECTIVES Religious fasting (RF) is practiced annually by millions of Christian and Muslim followers worldwide. Scarce data exist on the impact of RF on the metabolic and hematological profile of individuals with or without dyslipidemia. SUBJECTS/METHODS The present study included: (i) 60 Greek Orthodox participants, 30 with dyslipidemia and 30 without dyslipidemia, who abstained from meat, fish and dairy products for seven consecutive weeks, and (ii) 15 young, non-dyslipidemic Muslim participants abstaining totally from food and liquid from dawn till sunset during 30 days. Biochemical (iron, ferritin, vitamin B12, calcium, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglyceride and fasting glucose) and hematological (hemoglobin, hematocrit) serum blood test results of study participants were measured pre- and post- RF (at weeks 0 and 7 for Orthodox participants and at weeks 0 and 4 for Muslim participants). RESULTS In dyslipidemic and non-dyslipidemic Orthodox participants, a significant reduction of fasting glucose, HDL, LDL and TC levels was found post-RF. Hemoglobin, hematocrit, iron and ferritin levels were significantly increased, while post-RF vitamin B12 and calcium levels were substantially decreased. Subanalysis between dyslipidemic and non-dyslipidemic Orthodox participants revealed a greater decrease of cholesterol levels in the former. In Muslim participants, triglyceride, LDL and total cholesterol levels were increased post-RF (all p values < 0.05). CONCLUSIONS Our study adds to the existing literature evidence about the significant impact of RF on metabolic and hematological profiles of Orthodox and Muslim followers. The prevention of calcium and B12 deficiency during Orthodox RF by supplement consumption as well as the protection from dehydration and dysregulation of lipid metabolism during Ramadan RF should concern both clinicians and dietician nutritionists. Nevertheless, studies with larger sample size and/or long-term follow-up are warranted before reaching definite conclusions about the effects of RF on human health.

To determine the relationships between circulating sex hormone-binding globulin (SHBG) and oxidized low-density lipoprotein (ox-LDL), total oxidant status, total antioxidant capacity, oxidative stress index, malondialdehyde, and the high-density lipoprotein (HDL) inflammatory index in patients with polycystic ovary syndrome (PCOS) and to investigate the effect of oxidative stress on the expression of SHBG and its mechanism in HepG2 cells.Cross-sectional study.University hospital.A total of 533 women with PCOS and 292 control women were included.None.Circulating SHBG, hormones, and metabolic and oxidative stress indices were determined in all subjects. The effects of ox-LDL and ox-HDL on the mRNA and protein expression of SHBG and related transcription factors were observed in HepG2 cells.The HDL inflammatory index, total oxidant status, oxidative stress index, and malondialdehyde levels were significantly higher in the three PCOS subgroups with different SHBG levels than in the controls. The ox-LDL and total antioxidant capacity were higher in the PCOS subgroups with SHBG levels75th percentile compared with the controls or the PCOS subgroup with SHBG levels ≥75th percentile. In HepG2 cells, the SHBG concentration in the culture supernatant, the mRNA levels of SHBG and hepatocyte nuclear factor-4α (HNF-4α), and the protein levels of HNF-4α were significantly lower in ox-LDL- and ox-HDL-treated cells than in the control cells and lipoprotein-treated cells.Oxidative stress inhibits the expression and secretion of SHBG by downregulating HNF-4α in vitro and may be an important factor promoting the occurrence of hyperandrogenemia in PCOS.

Introduction Poor oral health can negatively affect general health and quality of life of kidney transplant recipients. The study aimed to investigate the association between chronic oral disease burden, serum biomarkers, and comorbidities in kidney transplant recipients. Design A cross-sectional comparative study was conducted with 44 patients after kidney transplant. The burden of chronic oral disease was composed of the following observable variables: moderate periodontitis and presence of dental caries. Serum biomarkers and comorbidities data were collected. The chi-square or Fisher's exact tests for categorical variables and Student's t-test or Mann–Whitney test for continuous variables were used. Robust Poisson regression was used to model the association. Results Higher levels of mean uric acid ( P = .01) and creatinine ( P = .03) were observed in the group of patients with oral disease burden, while the highest level of high-density lipoprotein was observed in the group without oral disease. Higher values of uric acid were associated with the occurrence of chronic oral disease burden (Adjusted PR = 1.24, 95% CI: 1.03-1.48, P = .019). There was no statistical difference between the groups with and without oral disease burden in comorbidities present. Conclusion The findings suggest that chronic oral diseases burden can be associated with uric acid and creatinine levels in kidney transplant recipients.

Amiodarone and its main metabolite, desethylamiodarone, are highly distributed to serum lipoproteins such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone and desethylamiodarone with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Total serum concentrations of amiodarone and desethylamiodarone were examined in 116 patients receiving amiodarone for tachyarrhythmias. The concentration-to-dose (C/D) ratio of amiodarone positively correlated with the level of serum triglyceride (rs = 0.541, P < 0.001) and was higher in the hypertriglyceridemic state than in normotriglyceridemic state (479 ± 211 vs. 320 ± 161, P < 0.001). No correlation was found between the C/D ratio of desethylamiodarone and serum triglyceride levels (rs = 0.272), although higher values were observed in the hypertriglyceridemic state (322 ± 125 vs. 285 ± 143, P < 0.001). In hypertriglyceridemic state, the distribution of amiodarone increased in LDL/VLDL fraction and decreased in high-density lipoprotein and albumin fractions. The ratio of serum amiodarone to serum desethylamiodarone, a metabolic ratio of amiodarone, positively correlated with serum triglyceride levels (rs = 0.572, P < 0.001) and was higher in hypertriglyceridemic state, suggesting that amiodarone metabolism decreased in hyperlipidemia. The results of this study reveal that serum concentrations of amiodarone increase in hypertriglyceridemic state through the increased lipoproteins-binding and decreased metabolism of amiodarone.

Proprotein convertase subtilisin/kexin type 9 (Pcsk9) binds to hepatic low-density lipoprotein receptor (LDLR) and induces its internalization and degradation. Pcsk9 inhibition increases LDLR expression by hepatocytes, which causes increased uptake of circulating LDL, thereby reducing plasma LDL-cholesterol. However, by increasing the uptake of LDL by the liver, Pcsk9 inhibition increases the exposure of the liver to cholesterol, which may result in higher risk of steatohepatitis and ever carcinogenesis. We compared Pcsk9-/- knockout (KO) mice and appropriate wild-type (WT) controls of the same strain assigned to a high-fat (15%, wt/wt) diet for 9 months supplemented with 0.25%, 0.5%, or 0.75% dietary cholesterol. Pcsk9 KO mice on a high-fat, high-cholesterol diet exhibited higher levels of hepatic free cholesterol loading and hepatic cholesterol crystallization than their WT counterparts. Pcsk9 KO mice developed crown-like structures of macrophages surrounding cholesterol crystal-containing lipid droplets and hepatocytes, exhibited higher levels of apoptosis, and developed significantly more hepatic inflammation and fibrosis consistent with fibrosing steatohepatitis, including 5-fold and 11-fold more fibrosis at 0.5% and 0.75% dietary cholesterol, respectively. When injected with diethylnitrosamine, a hepatic carcinogen, early-in-life Pcsk9 KO mice were more likely to develop liver cancer than WT mice. Conclusion: Pcsk9 KO mice on high-cholesterol diets developed increased hepatic free cholesterol and cholesterol crystals and fibrosing steatohepatitis with a higher predisposition to liver cancer compared with WT mice. Future studies should evaluate whether patients on long-term treatment with anti-PSCK9 monoclonal antibodies are at increased risk of hepatic steatosis, steatohepatitis or liver cancer, while accounting for concurrent use of statins.

The present study aimed to evaluate the influence of dietary supplementation of different levels of L-carnitine and/or lysine-methionine (Lys-Met) on reproductive performance of breeder ducks. Three L-carnitine (0, 75 and 150 mg/kg) and three lysine-methionine (100%, 110% and 120% above the NRC (Nutrient requirements of poultry, 1994, National Academy Press) recommendations) levels were fed to 180 breeder ducks (144 females and 36 males) in a completely randomized design for 49 days. Laying performance and reproductive traits were evaluated; additionally, uric acid, total protein total, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed. The Lys-Met above 100% NRC (Nutrient requirements of poultry, 1994, National Academy Press) recommendations with or without L-carnitine improved feed utilization (p .05). Furthermore, Lys-Met above 100% recommendations without L-carnitine improved egg fertility and hatchability. Fertility and hatchability improved in breeders fed on L-carnitine with 120% Lys-Met (p .05). Serum glucose increased and total cholesterol reduced on 100% Ly-Met without L-carnitine or 110% Ly-Met with 150 mg L-carnitine (p .05). Glucose was reduced, while total cholesterol increased on 75 mg L-carnitine and 100% Lys-Met (p .05). Increasing Lys-Met without L-carnitine reduced serum protein (p .05). Albumin and ALT increased on 75 mg L-carnitine-100% Lys-Met and reduced on 150 mg L-carnitine-120% Lys-Met (p .05). There were no interaction effects on globulin, uric acid and AST (p .05). Thus, based on findings, breeder ducks responded to dietary Lys-Met more efficiently than L-carnitine; however, more research is needed to evaluate also economic aspects related to L-carnitine dietary supplementation.

Objective. To investigate association of incidence between pancreatic adipose infiltration and metabolic syndrome (METS). Methods. We searched PubMed, Embase, Cochrane Library, and Web of Science databases up to July 2021. We compared incidence rate of METS between adults with and without pancreatic adipose infiltration, along with their clinical features, such as fasting blood glucose (FBG), triglyceride (TG), high-density lipoprotein (HDL), and hypertension (HTN). Cross-sectional study, cohort study, and case control study were included. Two investigators independently completed study selection, data extraction, and risk of bias assessment. Results. Eleven eligible studies that involved 17,127 patients were included, including 8 cross-sectional studies, 2 cohort studies, and 1 case control study. There was a trend of increasing in incidence rate of METS ( OR = 2.66 , 95% CI: 1.89-3.75) of adults with pancreatic adipose infiltration when compared to those without the disease. There was a trend of increasing in HTN ( OR = 1.68 , 95% CI: 1.32-2.13) and levels of FBG ( SMD = 0.54 , 95% CI: 0.35-0.72) and TG ( SMD = 0.39 , 95% CI: 0.25-0.53) of adults with pancreatic adipose infiltration, while there was a trend of decreasing in HDL level ( SMD = − 0.29 , 95% CI: -0.43~ -0.15). Conclusion. There was an association of incidence between pancreatic adipose infiltration and METS. Indicators of clinical features related to pancreatic adipose infiltration were more likely to arise, such as FBG and TG levels and HTN, but HDL level tended to decrease.

Objectives Cholesterol efflux capacity (CEC), an atheroprotective function of high-density lipoprotein, is expected to be a potential biomarker for cardiovascular disease. However, CEC has not been widely introduced for application in clinical laboratories because of the complexity of the conventional CEC assay using cells and radioactive materials. Previously, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILG), which solves these issues. We aimed to confirm the validation and further improve the ILG method for application in the clinical setting. Methods Cholesterol efflux capacity values by the ILG method assayed for shorter incubation time (4 h) were compared to those assayed for 16 h (our previous ILG method). To investigate a reference material that can correct the variation between ILG manufacturing lots, bovine serum albumin, human gamma-globulins, and globulin complexes were evaluated. CEC values were also estimated in plasmas obtained with different anticoagulants, serum treated with freeze-thaw cycles, and serum mixed with several interference substances. Results The CEC of 4- and 16-h incubation times were well correlated. Globulin complexes may be used as a reference material. Plasma can be used as the specimen. The serum and stored temperature of the specimen did not largely affect CEC. Hemoglobin and chyle did not have an effect on CEC, whereas high-bilirubin serum showed elevated CEC. The effect of bilirubin was nearly canceled by subtracting basal fluorescence intensity. Conclusions Present ILG method further fulfills some requirements for application in clinical laboratory. Using this reliable simple method, evaluation for clinical significance of CEC is expected.

Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.

AIMS/INTRODUCTION Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied. MATERIALS AND METHODS Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate 300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay. RESULTS The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria. CONCLUSIONS Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Supplemental Digital Content is available in the text., Objective: We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity. Approach and Results: The participants (36 subjects; age, 48±10 years; body mass index, 30.9±6.2 kg/m2) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group. Conclusions: The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans. Registration: URL: http://www.clinicaltrials.gov; Unique identifier NCT02133144.

Background Alcohol-associated liver disease (ALD) and alcoholic hepatitis (AH) significantly impact the liver, an organ central to the lipid and lipoprotein metabolism. Objective To define changes in the lipid and lipoprotein profiles in subjects with alcoholic hepatitis (AH) versus heavy drinkers with normal liver function and to determine the association of the AH-mediated lipoprotein phenotype with AH severity and outcomes. Methods AH cases (n=196) and a heavy drinker control group (n=169) were identified in a multicenter, prospective cohort. The relationships between lipid panels and lipoprotein profiles among AH and heavy drinkers were interrogated using three common measurements: the conventional lipid panel, extended lipid panel by NMR, and NMR-based direct lipoprotein profiling. Predictive values for AH severity and mortality were determined using Harrell's C-Index. Results Lipid and lipoprotein profiles were significantly different in AH compared to heavy drinkers. Among them, high density lipoprotein (HDL) particle concentration exhibited the most significant reduction in AH compared to heavy drinkers (5.3 ± 3.4 vs 22.3 ± 5.4 μmol/L, p Conclusion Lipid and lipoprotein profiles are profoundly altered in AH and can help in prognosticating disease severity and mortality.

Background Although renal insufficiency and dyslipidemia are known to be closely associated, the effect of kidney function on the size and clinical value of high-density lipoprotein (HDL) particles remains largely unknown, especially in patients with coronary heart disease. Methods A total of 419 coronary heart disease patients and 105 non-coronary heart disease patients were included. HDL particle size, represented by HDL-C/apoA-I, was compared between groups stratified by estimated glomerular filtration rate (eGFR) and Gensini scores using standard Student’s t test and one-way ANOVA. Pearson’s correlation test was performed to analyze the association between eGFR and HDL-C/apoA-I in patients with coronary heart disease. The relationship between HDL particle size and the occurrence of coronary heart disease was explored using Univariate logistic regression analysis. Results In patients with coronary heart disease, between-group analysis revealed that HDL-C/apoA-I increased as eGFR declined, and significance appeared as eGFR declined to under 60 ml/min·1.73 m2 (P 2), those with higher Gensini scores had smaller HDL-C/apoA-I. However, with or without kidney insufficiency, smaller HDL-C/apoA-I was associated with a higher occurrence of coronary heart disease (P Conclusion With the presence of renal insufficiency, HDL-C/apoA1 was higher in patients with coronary heart disease. Lower HDL-C/apoA1 was still associated with a higher occurrence of coronary heart disease, but the original association between lower HDL-C/apoA1 and more severe coronary artery stenosis was lost in patients with renal insufficiency.

Familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), and elevated lipoprotein (a) (Lp[a]) increase risk of premature coronary artery disease (CAD). The objective of this study was to assess the prevalence of FH, FCHL, elevated Lp(a) and their impact on management in patients with premature CAD.We prospectively recruited men ≤ 50 years and women ≤ 55 with obstructive CAD. FH was defined as Dutch Lipid Clinic Network scores ≥ 6. FCHL was defined as apolipoprotein B1.2 g/L, triglyceride and total cholesterol90th population percentile, and family history of premature cardiovascular disease. Lp(a) ≥ 50 mg/dL was considered to be elevated.Among 263 participants, 9.1% met criteria for FH, 12.5% for FCHL, and 19.4% had elevated Lp(a). Among patients with FH, 37.5% had FH-causing DNA variants. Patients with FH, but not other dyslipidemias, were more likely than nondyslipidemic patients to have received lipid-lowering therapy before presenting with CAD (33.3% vs 12.3%, P = 0.04) and combined lipid-lowering therapy after the presentation (41.7% vs 7.7%, P0.001). One year after presentation, 58.3%, 54.5%, and 58.8% of patients with FH, FCHL, and elevated Lp(a) had low-density lipoprotein cholesterol (LDL-C)1.8 mmol/L, respectively, compared with 68.0 % in reference group. Patients with FCHL were more likely to have non-high-density lipoprotein (HDL) and apolipoprotein B above recommended lipid goals (70.0% and 87.9%, respectively).FH, FCHL, and elevated Lp(a) are common in patients with premature CAD and have differing impact on treatment and achievement of lipid targets. Assessment for these conditions in patients with premature CAD provides valuable information for individualized management.

A model to quantitatively characterize the effect of evinacumab, an investigational monoclonal antibody against angiopoietin‐like protein 3 (ANGPTL3) on lipid trafficking is needed. A quantitative systems pharmacology (QSP) approach was developed to predict the transient responses of different triglyceride (TG)‐rich lipoprotein particles in response to evinacumab administration. A previously published hepatic lipid model was modified to address specific queries relevant to the mechanism of evinacumab and its effect on lipid metabolism. Modifications included the addition of intermediate‐density lipoprotein and low‐density lipoprotein compartments to address the modulation of lipoprotein lipase (LPL) activity by evinacumab, ANGPTL3 biosynthesis and clearance, and a target‐mediated drug disposition model. A sensitivity analysis guided the creation of virtual patients (VPs). The drug‐free QSP model was found to agree well with clinical data published with the initial hepatic liver model over simulations ranging from 20 to 365 days in duration. The QSP model, including the interaction between LPL and ANGPTL3, was validated against clinical data for total evinacumab, total ANGPTL3, and TG concentrations as well as inhibition of apolipoprotein CIII. Free ANGPTL3 concentration and LPL activity were also modeled. In total, seven VPs were created; the lipid levels of the VPs were found to match the range of responses observed in evinacumab clinical trial data. The QSP model results agreed with clinical data for various subjects and was shown to characterize known TG physiology and drug effects in a range of patient populations with varying levels of TGs, enabling hypothesis testing of evinacumab effects on lipid metabolism.

Background Obesity is one of the most challenging clinical syndromes associated with deleterious health problems. Waist-to-height ratio (WHtR), a newer index for abdominal fat assessment, can be a superior tool in the evaluation of cardiometabolic risk. This study aimed to determine the relation between WHtR and lipid cardiovascular risk ratios and insulin resistance (IR) in children and adolescents with exogenous obesity. Results This analytical cross-sectional study included 80 children and adolescents with exogenous obesity, compared to 80 age- and sex-matched healthy non-overweight non-obese controls. Fasting lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL)), fasting insulin, and fasting blood glucose were done and lipoprotein risk ratios were calculated; TC/HDL, LDL/HDL, non-HDL/HDL, and TG/HDL). In addition, homeostatic model assessment for IR (HOMA IR), triglyceride glucose index (TyG), TyG-BMI, and TyG-WC were calculated. The study group included 55 (34.4%) males and 105 (65.6%) females with a mean age of 13.6 ± 2.22 years. Obese group had significantly higher TC, TG, LDL, non-HDL, LDL/HDL, TC/HDL, non-HDL/HDL, and TG/HDL, with significantly lower HDL. In addition, they had significantly higher FBG, HOMA IR, TyG, TyG-BMI, and TyG-WC indices compared to the control group. There were statistically significant correlations between WHtR and lipid profile, lipid risk ratios and indices of IR. WHtR was found to be an independent predictor of IR by linear regression analysis. Conclusion WHtR can be an excellent, easy, and reliable clinical predictor for cardiovascular risk and IR in children and adolescents with exogenous obesity.

Graphical abstract, Cholesterol has been shown to affect the extent of coronavirus binding and fusion to cellular membranes. The severity of Covid-19 infection is also known to be correlated with lipid disorders. Furthermore, the levels of both serum cholesterol and high-density lipoprotein (HDL) decrease with Covid-19 severity, with normal levels resuming once the infection has passed. Here we demonstrate that the SARS-CoV-2 spike (S) protein interferes with the function of lipoproteins, and that this is dependent on cholesterol. In particular, the ability of HDL to exchange lipids from model cellular membranes is altered when co-incubated with the spike protein. Additionally, the S protein removes lipids and cholesterol from model membranes. We propose that the S protein affects HDL function by removing lipids from it and remodelling its composition/structure.

We explore miR‐150‐5p in atherosclerosis (AS). The AS model was constructed using Apo E−/− mice with an injection of the miR-150-5p mimic or an inhibitor. Pathological characteristics were assessed using Oil red O staining and Masson staining. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expressions of microRNA-150-5p (miR-150-5p), STAT1, α-SMA (α-smooth muscle actin) and proliferating cell nuclear antigen (PCNA). Targetscan and dual-luciferase reporter assay were used to analyze the interaction between miR-150-5p and STAT1. The viability, migration, cell cycle and α-SMA and PCNA expressions in oxidized low-density lipoprotein (ox-LDL)-stimulated primary human aortic smooth muscle cells (ASMCs) were assessed using molecular experiments. miR-150-5p was reduced in both AS mice and ox-LDL-stimulated human aortic smooth muscle cells but STAT1 had the opposite effect. The miR‐150‐5p inhibitor alleviated the increase of lipid plaque and reduced collagen accumulation in the aortas during AS. Upregulation of α-SMA and PCNA was reversed by miR-150-5p upregulation. STAT1 was targeted by miR‐150‐5p, and overexpressed miR-150-5p weakened the ox-LDL-induced increase of viability and migration abilities and blocked cell cycle in ASMCs, but overexpressed STAT1 blocked the effect of the miR‐150‐5p mimic. This paper demonstrates that miR-150-5p has potential as a therapeutic target in AS, with plaque stabilization by regulating ASMC proliferation and migration via STAT1.

Background Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. Methods Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. Results In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. Conclusions The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

Emerging evidence suggests that elevated concentrations of triglyceride-rich lipoprotein remnants (TRLs) derived from hepatic and intestinal sources contribute to the risk of atherosclerotic cardiovascular events. Natural selection studies support a causal role for elevated concentrations of remnant cholesterol and the pathways contributing to perturbations in metabolic pathways regulating TRLs with an increased risk of atherosclerotic cardiovascular disease events. New therapies targeting select catalytic pathways in TRL metabolism reduce atherosclerosis in experimental models, and concentrations of TRLs in patients with a vast range of triglyceride levels. Clinical trials with inhibitors of angiopoietin-like 3 protein and apolipoprotein C-III will be required to provide further guidance on the potential contribution of these emerging therapies in the paradigm of cardiovascular risk management in patients with elevated remnant cholesterol.

PURPOSE Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), which is still a major reason for blindness. Transthyretin (TTR) and retinol-binding protein (RBP) are thought to be related to the pathogenesis both in T2DM and T1DM. We aimed to investigate the association between serum levels of TTR, RBP, RBP/TTR ratio, and DR. METHODS This retrospective study involved 188 T1DM inpatients divided into two groups: patients with DR (n = 95) and patients without DR (n = 93). Data of serum levels on lipids and inflammation were collected. Multiple logistic regression analysis was performed to research the association between TTR, RBP, RBP/TTR, and diabetic retinopathy in T1DM. RESULTS Compared with patients without DR, those with DR have a higher level of TTR (207 versus 195 mg/L, p = 0.034) and RBP4 (36.85 versus 25.68 mg/L, p

Introduction. Chromium (VI) is a common component of emissions from woodworking enterprises and an extremely dangerous polytropic toxic chemical substance that has a sensitizing, mutagenic and carcinogenic effect. The aim of the study was to assess disorders of critical organs and systems in children with an increased chromium content in the blood. Materials and methods. The content of chromium in the blood was investigated, the values ​​of clinical and biochemical parameters were estimated, the statistical processing of the data was carried out using the Statistica 10 software. Results. The level of chromium in the blood of children from the observation group was 2.4 times higher than in the control group. In children with an increased concentration of chromium in the blood, compared with children in the control group, a significant increase in IgE of total, eosinophilic-lymphocytic index, total and direct bilirubin, low-density lipoprotein, α-amylase and LDH was found to be higher by 1.2-3.1 times. TSH, and a 1.2-fold lowering of HDL cholesterol. Significant relationships were obtained between an increased concentration of chromium in the blood and an increased level of IgE total, eosinophilic-lymphocytic index, α-amylase and TSH (R 2 = 0.20-0.31, p

INTRODUCTION Bariatric surgery is considered an effective treatment for weight loss and for improving the metabolic profile of patients with obesity. Obesity-related comorbidities such as hyperlipidaemia and type 2 diabetes mellitus (DM) are significant cardiovascular risk factors. Additionally, prospective clinical trials have shown that statins increase the risk of development of DM, and many patients with obesity are on statins. We retrospectively examined the effect of bariatric surgery on lipid profile, DM control and weight loss at the five-year follow-up. METHODS In total, 104 patients undergoing bariatric surgery from 2008 to 2012 were retrospectively studied. 36 patients were on preoperative statins. Their lipid profile, DM control and weight loss were examined at the one-year and five-year follow-ups. RESULTS Both high-density lipoprotein and triglyceride levels showed significant improvement at the one-year and five-year follow-ups (p = 0.01). Total cholesterol showed significant improvement at the one-year follow-up (−0.30 mmol/dL, p = 0.0338); however, better control was not sustained at the five-year follow-up (−0.15 mmol/dL, p = 0.133). Low-density lipoprotein did not show any considerable improvement at the one- and five-year follow-ups (−0.27 mmol/dL, p = 0.150 and −0.24 mmol/dL, p = 0.138, respectively). A statistically significant improvement in DM control was observed in these patients and in those on preoperative statins. Weight loss was sustained at one and five years. CONCLUSION Bariatric surgery does not confer a uniform improvement in lipid profile in the long term. It does, however, induce efficient weight loss and improvement in diabetic profile, even in patients on preoperative statins.

Gestational diabetes mellitus (GDM) initiates when a woman’s pancreas could not act appropriately to bypass the diabetogenic condition during pregnancy. It is increasing across the world, including Bangladesh. Triglycerides (TG) and high-density lipoprotein-cholesterol (HDLC) are strongly connected with insulin resistance in pregnant women. Observation of the role of lipid profiles and TG/HDL cholesterol ratio associated with fasting glucose in GDM subjects. In this experiment, a total of 232 individual subjects consisting of 132 GDM-positive and 100 GDM-negative pregnant women were examined and observed from 24 to 28 weeks of their pregnancy period. For this study, we had collected blood samples from selected women before and after breakfast and analyzed blood glucose level, triglyceride cholesterol level, HDL, low-density lipoprotein (LDL), and TG/HDL ratio. TG and LDL-cholesterol were significantly higher (p

This study aimed to assess the growth performance and blood metabolites, as well as metabolic profiles in the urine of lambs fed on dietary rumen-protected choline (RPC). Thirty-six Dorper × Hu lambs weighing approximately 20 kg were equally assigned to three groups, and fed on three diets supplemented with different RPC concentrations (0, 0.25% and 0.75%) for 45 days. Supplementation of RPC significantly increased average daily gain (ADG) and decreased feed-to-gain ratio (F/G) of lambs (p

The functional characteristics of Lactobacillus johnsonii BFE6154, first isolated from Maasai traditional fermented milk, were previously identified in vitro, but its cholesterol-lowering properties have not been verified yet. In this study, we investigated the effect of L. johnsonii BFE6154 on cholesterol regulation and the mode of action. Stimulation of Caco-2 intestinal epithelial cells with L. johnsonii BFE6154 downregulated the gene expression of Niemann-Pick C1-like 1 (NPC1L1) through the activation of liver X receptor (LXR). Also, stimulation of HepG2 cells with the metabolites produced by L. johnsonii BFE6154 revealed an increase in the gene expression of low-density lipoprotein receptor (LDLR). Oral administration of L. johnsonii BFE6154 in mice receiving a high-fat and high-cholesterol diet (HFHCD), reduced total cholesterol and low-density lipoprotein-cholesterol (LDL) and increased high-density lipoprotein-cholesterol (HDL) in the blood, compared to the control. Diet-induced hypercholesterolemic mice receiving L. johnsonii BFE6154 showed a suppression of cholesterol absorption under the control of NPC1L1 in the intestine. Furthermore, L. johnsonii BFE6154 consumption ameliorated the hepatic cholesterol level and LDLR expression, which was reduced by HFHCD. These molecular modulations led to the increase of cholesterol excretion and the decrease of cholesterol levels in the feces and liver, respectively. Taken together, these results suggest that L. johnsonii BFE6154 may protect against diet-induced hypercholesterolemia through the regulation of cholesterol metabolism in the intestine and liver.

A randomized clinical trial high-density lipoprotein (HDL) cholesterol uptake capacity (CUC) is reduced in patients with metabolic syndrome (MetS). We have assessed the effect of crocin supplementation on HDL CUC in patients with MetS. Forty-four subjects with MetS were randomly allocated to one of two groups: one group received placebo and the other group received crocin at a dose of 30 mg (two tablets of 15 mg per day) for 8 weeks. Serum biochemical parameters were measured using an AutoAnalyzer BT3000 (BioTechnica). The modified CUC method is a cell free, simple, and high-throughput assay that used to evaluate HDL CUC of serum samples. The decision tree analysis was undertaken using JMP Pro (SAS) version 13. The mean age of the crocin and placebo groups were 38.97 ± 13.33 and 43.46 ± 12.77 years, respectively. There was a significant increase in serum HDL CUC in the crocin group compared to that of the placebo group in patients with MetS (p-value< 0.05). The decision tree analysis showed that serum HDL functionality was more important variable than HDL-C level in predicting patients with hypertension at baseline (p-value < 0.05). Crocin administration (30 mg for a period of 8 weeks) was found to improve serum HDL CUC in patients with MetS. Trial registration: IRCT2013080514279N1.

Background Non-alcoholic fatty liver disease (NAFLD) patients are at a substantial risk for developing cardiovascular disease (CVD). High-density lipoprotein (HDL) is well known to have protective effects against the development of atherosclerotic CVD. One of the major antiatherogenic effects of HDL is its anti-oxidative function. Objectives This study investigated the association of anti-oxidative capacity of HDL with subclinical atherosclerosis in NAFLD and non-NAFLD subjects. Methods A total of 143 subjects including 51 NAFLD and 92 control subjects were included in this case–control study. HDL oxidative index (HOI) was determined spectrophotometrically using a cell-free method in the presence of a fluorescent substrate dichlorofluorescein diacetate (DCFDA). Paraoxonase 1 (PON1) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) plasma levels were assessed in both groups. Results The NAFLD patients with impaired HDL anti-oxidative function (HOI ≥ 1) had higher MDA levels, aspartate amino transferase (AST), liver stiffness (LS), and carotid intima-media thickness (cIMT) values compared to the controls. HDL oxidative index (HOI) was positively correlated with MDA levels and cIMT and negatively correlated with SOD activity. Conclusions Higher circulating levels of MDA were associated with the impaired anti-oxidative function of HDL in NAFLD. The impaired anti-oxidative capacity of HDL might be related to NAFLD severity and subclinical atherosclerosis in NAFLD patients.

Context Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. Objective We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. Methods This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. Results During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = −0.41; P = 0.002), and CRP (r = −0.28; P = 0.041). Conclusion Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.

Background: Peripheral arterial disease (PAD) is common in patients with end-stage renal disease on hemodialysis, but is frequently underdiagnosed. The risk factors for PAD are well known within the general population, but they differ somewhat in hemodialysis patients. This study aimed to determine the prevalence of PAD and its risk factors in patients on hemodialysis. Objective: To assess the prevalence of peripheral arterial disease in end stage renal disease patients on hemodialysis. Patients and Methods: This was across-sectional study carried out at Hemodialysis Unit of Al-Hussein University Hospital over a period of six month; from September 2019 to April 2020, and conducted on 80 hemodialysis patients. Demographic data and clinical information were recorded. Laboratory data including CBC, calcium, phosphate, total cholesterol, triglyceride, high-density lipoprotein, and iron profile were evaluated. The ankle-brachial index was measured in all patients. PAD was diagnosed if ankle-brachial index 0.9. Results: As regard description of demographic data, the mean age of all studied patients was 45.3 ± 8.8 years with minimum age of 24 years and maximum age of 62 years. There were 43 males (53.8%) and 37 females (46.3%). Thirty-five patients (43.7%) were diabetic, and 48 patients (60%) were hypertensive. According to laboratory profile, the mean of WBCs, Hb, platelets, serum calcium, PO4, and iPTH were 6.5 x10³/ul, 10.4 g/dl, 228.2 x10³/ul, 8.3 mg/dl, 9.4 mg/dl and 477.2 ug/ml respectively. Regarding lipid profile, the mean of total cholesterol, HDL and triglyceride were 214.7 mg/dL, 41.9 mg/dL,and 172.2 mg/dL, respectively. Regarding to iron profile, the mean of iron serum, ferritin and TIBC were 62.7 mg/dl, 603.3 ng/ml and 236.7 mg/dl, respectively. According to ABI, there were 22 patients (27.5%) ≤ 0.9, while there were 58 patients (72.5%) > 0.9. The prevalence of peripheral arterial disease among HD patients was 27.5%. Conclusions: High prevalence of peripheral arterial disease in CKD patients on hemodialysis and Ankle –brachial index was clearly more sensitive than physical examination in detecting of peripheral arterial disease in CKD patients on hemodialysis.

The inverse correlation between high-density lipoprotein (HDL) levels in vivo and the risk of Alzheimer's disease (AD) has become an inspiration for HDL-inspired AD therapy, including plain HDL and various intelligent HDL-based drug delivery systems. In this review, we will focus on the two endogenous HDL subtypes in the central nervous system (CNS), apolipoprotein E-based HDL (apoE-HDL) and apolipoprotein A-I-based HDL (apoA-I-HDL), especially their influence on AD pathophysiology to reveal HDL's potential as biomarkers for risk prediction, and summarize the relevant therapeutic mechanisms to propose possible treatment strategies. We will emphasize the latest advances of HDL as therapeutics (plain HDL and HDL-based drug delivery systems) to discuss the potential for AD therapy and review innovative techniques in the preparation of HDL-based nanoplatforms to provide a basis for the rational design and future development of anti-AD drugs.

Fermentation strategy is well documented to improve the nutritional value of agricultural waste by-products such olive cake (OC), which, in turn, provides healthy, safe, and affordable feedstuff. This study assessed the combined impact of Aspergillus oryzae-fermented OC (AFOC) on the growth performance, intestinal morphometry, blood biochemistry, lysozyme activity, gut immune-related genes, and flesh quality of Nile tilapia. We divided 225 fish into five groups and further subdivided into three replicates (n = 15 each) and fed them five diets (Control, AFOC5, AFOC10, AFOC15, AFOC20) to determine AFOC nutritional value and its optimized incorporation level in the diet. The trial continued for 3 months. The crude protein content of OC improved by 7.77% after A. oryzae fermentation, while lipid content decreased by 14.19%. In addition, growth and feed utilization significantly improved at (10.8–11.2) % AFOC dietary level. High-density lipoprotein (HDL) significantly improved, and the serum lysozyme level was significantly higher in the AFOC10 group compared to other groups. Interestingly, gut-related inflammatory cytokines tumor necrosis factor alpha (TNF- α) and interleukin 1 beta (IL-1β) revealed higher relative mRNA expression in the AFOC10 group compared to other groups. The histomorphometric parameters was greatly influenced by the AFOC incorporation level (10%–20%). These findings suggested that A. orzae fermentation modifies the nutritional quality of OC, as seen through its positive impact on the growth performance, local and systemic immunity, and intestinal absorptive capacity of Nile tilapia. The recommended dose for dietary AFOC was around 11%

Lipoprotein(a) (Lp(a)) is a prothrombotic and anti-fibrinolytic lipoprotein, whose role has not been clearly defined in the pathogenesis of coronavirus disease 2019 (COVID-19). In this prospective observational study, serum Lp(a) as well as outcomes were measured in 50 COVID-19 patients and 30 matched sick controls. Lp(a) was also assessed for correlation with a wide panel of biomarkers. Serum Lp(a) did not significantly differ between COVID-19 patients and sick controls, though its concentration was found to be significantly associated with severity of COVID-19 illness, including acute kidney failure stage (r = 0.380, p = 0.007), admission disease severity (r = 0.355, p = 0.013), and peak severity (r = 0.314; p = 0.03). Lp(a) was also positively correlated with interleukin (IL)-8 (r = 0.308; p = 0.037), fibrinogen (r = 0.344; p = 0.032) and creatinine (r = 0.327; p = 0.027), and negatively correlated with ADAMTS13 activity/VWF:Ag (r = − 0.335; p = 0.021); but not with IL-6 (r = 0.241; p = 0.106). These results would hence suggest that adverse outcomes in patients with COVID-19 may be aggravated by a genetically determined hyper-Lp(a) state rather than any inflammation induced elevations. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02597-y.