Plasma High-density Lipoprotein Cholesterol Levels Research Articles

Synthesis of microwave-assisted carboxamides in Triton WR-1339-induced hyperlipidemic rats: possible hypolipidemic heterocyclic compounds.

The hypolipidemic effect of furan carboxamide derivatives was investigated using the Triton WR-1339 rat model. Nineteen compounds were synthesized, including furan-2-carboxamides of benzophenones and acetophenones (a(1-4)), anilines and amine derivatives (a(5-9)), picolinic-2-carboxamide derivatives of benzophenones and acetophenone (a(10-12)) and furan-2-carboxylate esters of benzophenones and acetophenones, substituted phenols and alcohols (b(1-7)). All the necessary steps were taken to synthesize, purify, and characterize these compounds. They were synthesized by reacting acyl chlorides of the heterocycles with their corresponding amines in the presence of pyridine and tert-butyl acetate. While the conventional heating method yielded acceptable yields for some of the reactions under reflux, the microwave synthesis reactor achieved significantly higher yields for others. Rats with hyperlipidemia were induced with Triton WR-1339 and then subjected to in vivo testing via an intraperitoneal injection of 200 mg kg-1 Triton WR-1339. The model was tested using an oral dose of bezafibrate (100 mg kg-1). After 7 hours of treatment with Triton, the new derivatives represented by compounds a(1-2), a(4-5), a7, and a(10-12) showed significant activity against the complete lipid profile, including a decrease in triglyceride, total cholesterol, and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol plasma levels. At 20 mg kg-1 dose, these compounds were superior to other lipid-lowering agents in reducing triglyceride levels and slightly increased high-density lipoprotein cholesterol levels. These results indicate a mutual mechanism of action of novel compounds with fibrates, where they have a marked effect on triglyceride and high-density lipoprotein cholesterol levels; for example, a5 causes a significant reduction (p 0.0001) of triglyceride levels by 86%, and a remarkable increase (p 0.0001) in high-density lipoprotein cholesterol plasma levels by 65% as compared to hyperlipidemic rats.

Comprehensive Assessment of the Safety of Eucommia ulmoides Leaf Extract for Consumption as a Traditional Chinese Health Food

To ensure the export quality of Eucommia ulmoides leaf extract (ELE) and facilitate E. ulmoides leaf inclusion in the directory of traditional Chinese health foods, an overall safety assessment of ELE was performed, including genotoxicity and long-term toxicity, according to the national food safety standards of China. No variations in the reverse mutation number of the nominal bacterial strains were observed under ELE treatment in comparison with the solvent control. Additionally, the micronucleus rates of in vivo mammalian erythrocytes and in vitro mammalian cells under ELE treatment were equivalent to or significantly lower than those of the solvent control. The fold change in the trifluorothymidine resistance mutation frequency of the thymidine kinase gene under ELE treatment was less than three times in comparison with the solvent control, suggesting that ELE did not cause genotoxicity. Moreover, animal experiments showed that the growth performance of rats under ELE treatment was enhanced because the body weights of rats increased. No oxidative injury or inflammatory responses were induced and no histopathological lesions of tissues were detected under ELE treatment. In addition, plasma triglycerides and low-density lipoprotein cholesterol levels significantly decreased, and plasma high-density lipoprotein cholesterol levels significantly increased with ELE treatment, suggesting that ELE was health-promoting. Furthermore, moderate to excellent antimicrobial activities, a favorable anticancer capacity, and superior antioxidant abilities of ELE were found, implying ELE possesses good bioactivities. Therefore, we affirmed ELE is safe to consume as a traditional Chinese health food.

Comparative Evaluation of Plasma Lipid Profile and Electrolytes in Diabetic and Non-Diabetic Individuals Attending Healthcare Checkup in Everight Laboratory in Owerri, Imo State, Nigeria

Background: Diabetes mellitus is a metabolic disorder characterized by abnormally high blood sugar which poses a serious challenge to public health globally. The measurement of blood sugar levels, serum lipid profiles, and electrolytes are essential in determining one's vulnerability to developing diabetic-related complications such as cardiovascular diseases.
 Aim: This was a comparative cross-sectional study designed to assess the dyslipidemia and electrolyte imbalance status of diabetic individuals attending routine healthcare checkups in Everight Diagnostic and Laboratory Services Limited, Owerri branch, using plasma lipid profile (total cholesterol, triglycerides, high-density lipoproteins and low-density lipoproteins) and electrolytes (sodium, potassium, chloride and bicarbonate) as markers.
 Methodology: A total of 120 participants consisting of 60 diabetics and 60 non-diabetic individuals were pooled for this study. From both groups, plasma samples upon centrifugation were used for the analyses of glucose, Total Cholesterol (TC), Triglycerides (TG), High-density lipoprotein cholesterol (HDL-C), Low-density Lipoprotein Cholesterol using Erba XL-200 auto biochemistry analyzer, and plasma Sodium (Na+), Potassium (K+), Chloride (Cl-), and Bicarbonate (HCO3-) using Audicom (AC9900) ion selective electrode (ISE) analyzer. Statistical analysis was carried out using version 20.0 and p- values less than 0.05 were considered statistically significant.
 Results: The demographic characteristics of the study population show 53% women, 47% men, and average age of 51.28. The fasting plasma glucose level of diabetic subjects (175.96 ± 91.62 mg/dL) was significantly higher (p<0.05) than the non-diabetic group (99.54 ± 11.50 mg/dL). More so, there were significant differences (p<0.05) between levels of TC (212.9 ± 56.65 mg/dL), TG (165.61 ± 89.05 mg/dL), and LDL-C (130. 59 ± 47.18 mg/dL) amongst diabetic individuals when compared with the levels of TC (169.87 ± 33. 57 mg/dL), TG (98.14 ± 39.14 mg/dL), and LDL (100.57 ± 27.78 mg/dL) of non-diabetic participants. Conversely, there was no significant difference when the plasma levels of HDL-C (52.78 ± 19.10 mg/dL), Na+ (136.93 ± 3.14 mmol/L), K+ (4.11 ± 0.54 mmol/L), HCO3- (22.03 ± 4.66 mEq/L) and Cl- (101.09 ± 4.33 mmol/L) of test subjects were compared with that of control individuals HDL-C (53.46 ± 15.04 mg/dL), Na+ (137.11 ± 3.37 mmol/L), K+ (4.17 ± 0.45 mmol/L), HCO3- (22.27 ± 3.55 mEq/L) and Cl- (94.52 ± 10.78) (p>0.05).
 Conclusion: The results of our study shows significant alteration of fasting lipid parameters amongst diabetics. This suggests that diabetic individuals are associated with dyslipidaemia, which predisposes them to cardiovascular risks.

Air Pollution: Another Threat to HDL Function.

Epidemiological studies have consistently demonstrated a positive association between exposure to air pollutants and the incidence of cardiovascular disease, with the strongest evidence for particles with a diameter < 2.5 μm (PM2.5). Therefore, air pollution has been included among the modifiable risk factor for cardiovascular outcomes as cardiovascular mortality, acute coronary syndrome, stroke, heart failure, and arrhythmias. Interestingly, the adverse effects of air pollution are more pronounced at higher levels of exposure but were also shown in countries with low levels of air pollution, indicating no apparent safe threshold. It is generally believed that exposure to air pollution in the long-term can accelerate atherosclerosis progression by promoting dyslipidemia, hypertension, and other metabolic disorders due to systemic inflammation and oxidative stress. Regarding high density lipoproteins (HDL), the impact of air pollution on plasma HDL-cholesterol levels is still debated, but there is accumulating evidence that HDL function can be impaired. In particular, the exposure to air pollution has been variably associated with a reduction in their cholesterol efflux capacity, antioxidant and anti-inflammatory potential, and ability to promote the release of nitric oxide. Further studies are needed to fully address the impact of various air pollutants on HDL functions and to elucidate the mechanisms responsible for HDL dysfunction.

164 HIGH HDL CHOLESTEROL INCREASES CARDIOVASCULAR RISK IN HYPERTENSIVE PATIENTS

Abstract Background Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. Methods To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. Results We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C&amp;lt;40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C&amp;gt;80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes (Figure 1). Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Conclusions Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Relation of Plasma High-Density Lipoproteins-Cholesterol with Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease

Background: Plasma high-density lipoproteins-cholesterol (HDL-C) is a marker of metabolic health; however, its association with age-associated muscle loss, termed sarcopenia, is unknown. We evaluated the clinical importance of HDL-C in predicting sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Methods: We investigated male healthy elderly and COPD patients, 54–79 years old (n = 55–59/group) through clinical examination, laboratory investigation, and spirometry. Sarcopenia was evaluated as low handgrip strength (HGS), appendicular skeletal mass index (ASMI), and gait speed. Enzyme-linked immunosorbent assays were used to measure the circulating markers of inflammation (C-reactive protein [CRP]) and oxidative stress (8-isoprostanes). Results: The COPD patients exhibited reduced HGS, ASMI and gait speed, and higher CRP and 8-isoprostanes levels and incidence of sarcopenia than controls (all P < 0.05). Plasma HDL-C levels exhibited significant correlations with CRP, HGS, and 8-isoprostane levels (all P<0.05) but not with ASMI and gait speed in both cohorts. Additionally, plasma HDL-C was an independent predictor of sarcopenia in controls and COPD patients (AUC = 0.631, P<0.05). Conclusion: Altogether, our data show that plasma HDL-C levels are a valuable marker of muscle decline and sarcopenia in healthy elderly and patients with COPD.

Brain-specific loss of Abcg1 disturbs cholesterol metabolism and aggravates pyroptosis and neurological deficits after traumatic brain injury.

Based on accumulating evidence, cholesterol metabolism dysfunction has been suggested to contribute to the pathophysiological process of traumatic brain injury (TBI) and lead to neurological deficits. As a key transporter of cholesterol that efflux from cells, the ATP-binding cassette (ABC) transporter family exerts many beneficial effects on central nervous system (CNS) diseases. However, there is no study regarding the effects and mechanisms of ABCG1 on TBI. As expected, TBI resulted in the different time-course changes of cholesterol metabolism-related molecules in the injured cortex. Considering ABCG1 is expressed in neuron and glia post-TBI, we generated nestin-specific Abcg1 knockout (Abcg1-KO) mice using the Cre/loxP recombination system. These Abcg1-KO mice showed reduced plasma high-density lipoprotein cholesterol levels and increased plasma lower-density lipoprotein cholesterol levels under the base condition. After TBI, these Abcg1-KO mice were susceptible to cholesterol metabolism turbulence. Moreover, Abcg1-KO exacerbated TBI-induced pyroptosis, apoptosis, neuronal cell insult, brain edema, neurological deficits, and brain lesion volume. Importantly, we found that treating with retinoid X receptor (RXR, the upstream molecule of ABCG1) agonist, bexarotene, in Abcg1-KO mice partly rescued TBI-induced neuronal damages mentioned above and improved functional deficits versus vehicle-treated group. These data show that, in addition to regulating brain cholesterol metabolism, Abcg1 improves neurological deficits through inhibiting pyroptosis, apoptosis, neuronal cell insult, and brain edema. Moreover, our findings demonstrate that the cerebroprotection of Abcg1 on TBI partly relies on the activation of the RXRalpha/PPARgamma pathway, which provides a potential therapeutic target for treating TBI.

Early time-restricted feeding improves high-density lipoprotein amount and function in nonhuman primates, without effects on body composition.

Time-restricted feeding (TRF), whereby caloric intake is limited to a <12-hour window, is a potential regimen to ameliorate metabolic syndrome and cardiovascular disease (CVD) risk co-occurring with aging and with obesity. Early TRF (eTRF; early morning feeding followed by overnight fasting) times calorie consumption with hepatic circadian gene expression rhythms. Brief TRF trials demonstrate that high-density lipoprotein (HDL) cholesterol increases similar to diet/exercise interventions, which may impart beneficial CVD effects. Using a nonhuman primate (NHP) model, the efficacy of eTRF to raise HDL and increase plasma cholesterol efflux capacity (CEC) (primarily mediated by cholesterol efflux to HDL particles, a process that is inversely associated with CVD risk) was examined. Adult (8-16 years old, n=25) and geriatric (≥17 years old) NHPs were randomized to ad libitum feeding or eTRF for 12 months, and relevant body composition, glycemic control, and plasma HDL cholesterol levels and CEC were measured. Impaired CEC was found in geriatric NHPs. eTRF induced larger-sized HDL particles, increased HDL apolipoprotein A-1 content, lowered triglyceride concentrations, and increased plasma CEC (primarily to HDL particles) in both adult and geriatric NHPs without changes in glycemic control or body composition. A beneficial effect of eTRF on increasing HDL CEC in NHPs was demonstrated.

High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients.

Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension. To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy. We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients. Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.

Calcium pyruvate attenuates fat deposition by augmenting fatty acid oxidation and inhibiting glucose oxidation in juvenile large yellow croaker (Larimichthys crocea) consuming a high-fat diet

Calcium pyruvate (CP), known as an energetic aid, has been shown to enhance lipid utilization and prevent obesity in mammals. However, very few studies were conducted to evaluate the potential implications of CP for aquatic animals. This study examined the role of CP on fat deposition in large yellow croaker by feeding fish with high-fat diets containing four levels of dietary CP (0, 0.375%, 0.75% and 1.5%). After a 70-d feeding trial, fish fed higher doses of CP significantly decreased weight gain (WG) and hepatosomatic index (HSI). Lipid percentages and triglyceride (TG) contents of whole fish, liver and muscle were negatively correlated with dietary CP. Plasma TG, total cholesterol (TC), LDL-cholesterol (LDL-c) and non-esterified fatty acids (NEFAs) levels significantly decreased with increasing dietary CP, whereas plasma HDL-cholesterol (HDL-c) and β-hydroxybutyrate (β-HB) levels came to a climax in fish fed the 1.5% CP diet. The fish fed CP diets also exhibited smaller hepatic lipid droplet size. The expression of lipogenic genes (fatty acid synthase, fas; acetyl-CoA carboxylase, acc; diacylglycerol acyltransferase 2, dgat2) were significantly down-regulated in the liver and muscle of the CP-treated fish. Conversely, the expression of lipolytic genes (adipose triglyceride lipase, atgl; hormone-sensitive lipase, hsl; carnitine palmitoyltransferase 1, cpt1) were markedly elevated. This was accompanied by enhanced tricarboxylic acid (TCA) cycle capacity (citrate content; succinate dehydrogenase, SDH; malate dehydrogenase, MDH). Further Western blot analysis revealed that CP may dose-dependently induce phosphorylations of AMP-activated protein kinase (AMPK) and ACC in the liver and muscle, together with protein expression of CPT1 and fatty acid translocase 36 (CD36). Surprisingly, treatment with CP impaired glucose utilization, as evidenced by raised plasma glucose and weakened glucose metabolism-related enzymatic activities (hexokinase, HK; phosphofructokinase, PFK; pyruvate kinase, PK; pyruvate dehydrogenase, PDH) and gene expression (glucokinase, gk; hk; phosphofructokinase-liver type, pfkl; pyruvate kinase-muscle type, pkma) in the liver and muscle. Notably, increased plasma liver enzyme activities (alanine aminotransferase, ALT; aspartate aminotransferase, AST) and hepatic inflammation-related gene expression (interleukin-1 beta, il-1β and cyclooxygenase 2, cox-2) and reduced hepatic antioxidant capacity (total antioxidative capacity, T-AOC; catalase, CAT) were found in high-dose CP treatment. These findings indicated that dietary CP could attenuate fat deposition by stimulating β-oxidation through the AMPK-ACC-CPT1 cascade and inhibiting lipogenesis and glucose oxidation. Considering both lipid-lowering effect and growth performance, dietary supplementation with 0.375% ∼ 0.75% CP is suitable for alleviating fat deposition of juvenile large yellow croaker.

Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.

Evaluation of the toxicological effects of atrazine-metolachlor in male rats: in vivo and in silico studies.

The types and mechanisms of atrazine-metolachlor toxicity, an herbicide composed of atrazine (ATR) and metolachlor (MET), need to be further investigated. This study evaluated the toxic actions of ATR-MET by in vivo and in silico methods. Here, varying doses of ATR-MET were orally administered to rats once daily for twenty-one days using normal saline as control. Molecular docking was used to characterize the binding of ATR and MET with androgen receptor (AR) to predict their potential endocrine-disrupting effects, using testosterone as benchmark. ATR-MET-induced-testicular toxicity (reduced sperm motility, count, and daily sperm production and increased live/dead ratio) was accompanied with testicular oxidative stress (diminished level of reduced glutathione, activities of glutathione-S-transferase, superoxide dismutase and catalase and increased level of malondialdehyde). Furthermore, ATR-MET induced cardiovascular toxicity (increased levels of plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides) with concomitant induction of renal toxicity (increased plasma creatinine and urea levels), and hepatotoxicity (increased plasma bilirubin, alkaline phosphatase, acid phosphatase, alanine aminotransferase and aspartate aminotransferase). Binding energy and amino acid interactions from in silico study revealed that MET possessed endocrine-disrupting capacity. In conclusion, exposure to atrazine-metolachlor could promote cardiovascular, renal, hepatic, as well as reproductive impairment in experimental male albino rats.

Cholesterol efflux capacity of high-density lipoprotein particles is impaired in age-related macular degeneration patients with high plasma HDL-C levels

Background and Aims : Age-related macular degeneration (AMD) is a blinding disease initiated by the formation of fat globules, so-called drusen, in the retina. Epidemiological studies demonstrated an association between elevated plasma high-density lipoprotein-cholesterol (HDL-c) levels and AMD. This is in contrast to the risk of cardiovascular disease that is negatively associated with HDL-c levels. Among the genes linked with AMD, ABCA1, CETP, LIPC and APOE are related to the role of HDL in mediating cholesterol efflux from cells and consequently in reverse cholesterol transport.

Effects of alpha lipoic acid supplementation on serum lipid profile in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled clinical trial.

Alpha lipoic acid (ALA) is considered a strong antioxidant with anti-inflammatory properties. Moreover, a number of previous studies have shown its lipid-lowering properties. Therefore, we designed this study to investigate the effects of ALA on lipid profile in patients with metabolic syndrome (MetS), which can lead to an increased risk of cardiovascular disease (CVD) and premature mortality. A total 46 patients with MetS were randomly divided into two groups. They received either 600 mg ALA (n = 23) or 600 mg placebo (n = 23) for 12 weeks. The body weight, height, body mass index (BMI), waist circumference (WC), fasting blood sugar (FBS), hemoglobin A1C (HbA1c), and blood pressure (BP) were assessed at baseline of the study. Physical activity level and dietary intake were assessed at baseline and end of the study. Serum lipid profile including triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were measured before and after 12 weeks of intervention. Baseline characteristics were similar in the ALA and placebo groups (P > 0.05). However, there were statistically significant differences in plasma levels of TG (-36.82 ± 42.48 versus 6.15 ± 25.04 mg/dl, P = 0.001) and TC (-8.91 ± 20.65 versus 10.84 ± 22.97 mg/dl, P = 0.01) after 12 weeks between the ALA group and the placebo group. Yet, there were no statistically significant differences in plasma levels of HDL-C and LDL-C after 12 weeks between the ALA group and the placebo group. The results suggest that daily supplementation of 600 mg ALA for 12 weeks may improve the lipid profile in patients with MetS.

Lipid-Lowering Effects of Carob Extracts (Ceratonia siliqua): Proposed Mechanisms and Clinical Importance.

The global prevalence of dyslipidemia (elevated plasma levels of total cholesterol, LDL-Cholesterol, triglycerides, and lower plasma levels of HDL-Cholesterol) is constantly on the rise. Lately, carob pulp has been recognized as an effective natural product for the treatment of dyslipidemia. The two main components of the carob pulp, polyphenols, and insoluble fiber are believed to have beneficial effects on lipid metabolism. Studies on humans and animals confirmed its lipid-lowering effects. Several mechanisms have been proposed to explain this phenomenon, namely by affecting three organ systems: 1) gastrointestinal tract, 2) liver and 3) adipose tissue. Also, carob products have antioxidative, anti-inflammatory, and vascular-protective activity.

Effect of the ABCA1 agonist CS-6253 on amyloid-β and lipoprotein metabolism in cynomolgus monkeys

BackgroundInducing brain ATP-binding cassette 1 (ABCA1) activity in Alzheimer’s disease (AD) mouse models is associated with improvement in AD pathology. The purpose of this study was to investigate the effects of the ABCA1 agonist peptide CS-6253 on amyloid-β peptides (Aβ) and lipoproteins in plasma and cerebrospinal fluid (CSF) of cynomolgus monkeys, a species with amyloid and lipoprotein metabolism similar to humans.MethodsCS-6253 peptide was injected intravenously into cynomolgus monkeys at various doses in three different studies. Plasma and CSF samples were collected at several time points before and after treatment. Levels of cholesterol, triglyceride (TG), lipoprotein particles, apolipoproteins, and Aβ were measured using ELISA, ion-mobility analysis, and asymmetric-flow field-flow fractionation (AF4). The relationship between the change in levels of these biomarkers was analyzed using multiple linear regression models and linear mixed-effects models.ResultsFollowing CS-6253 intravenous injection, within minutes, small plasma high-density lipoprotein (HDL) particles were increased. In two independent experiments, plasma TG, apolipoprotein E (apoE), and Aβ42/40 ratio were transiently increased following CS-6253 intravenous injection. This change was associated with a non-significant decrease in CSF Aβ42. Both plasma total cholesterol and HDL-cholesterol levels were reduced following treatment. AF4 fractionation revealed that CS-6253 treatment displaced apoE from HDL to intermediate-density- and low density-lipoprotein (IDL/LDL)-sized particles in plasma. In contrast to plasma, CS-6253 had no effect on the assessed CSF apolipoproteins or lipids.ConclusionsTreatment with the ABCA1 agonist CS-6253 appears to favor Aβ clearance from the brain.

Increased BMI and Blood Lipids Are Associated With a Hypercoagulable State in the Moli-sani Cohort.

The coagulation system can be assessed by the thrombin generation (TG) assay, and increased TG peak height, endogenous thrombin potential (ETP), and velocity index are associated with an increased risk of thrombosis. Obesity had been reported to increase TG and is associated with dyslipidemia, which also predisposes to atherosclerotic cardiovascular disease (CVD). However, the effect of the blood lipid profile on TG has not been studied extensively. To gain more insight into the associations of TG, body mass index (BMI) and lipid profile, we studied TG in relation to these parameters in a large Italian population cohort, the Moli-sani study (N = 22,546; age ≥ 35 years; 48% men). TG was measured in plasma samples collected at the enrollment of subjects in the Moli-sani study. TG was triggered with 1 or 5 pM tissue factor, and TG parameters lag time, peak, ETP, time-to-peak (TTP) and velocity index (VI). Additionally, thrombomodulin was added to assess the function of the activated protein C system during TG. In both women and men, overweight (BMI 25–30 kg/m2) and obesity (BMI > 30 kg/m2) were significantly associated with higher ETP, peak and VI (all p < 0.001). High total cholesterol, triglycerides and LDL-cholesterol levels were significantly associated with increased ETP and peak (all p < 0.001). Linear regression analysis revealed that the ETP is positively associated with both plasma LDL and HDL cholesterol levels, whereas the velocity index is positively associated with HDL cholesterol. Additionally, ETP, peak and VI were significantly associated with the plasma triglycerides content. In conclusion, our study shows significant associations of high BMI and blood lipid levels with increased TG parameters, and this hypercoagulability may partly explain the increased risk of CVD in individuals with obesity and/or dyslipidemia.

The Effect of Pre-transplant Lipid Profile on Post-transplant Hepatocellular Carcinoma Recurrence: Retrospective Single-Center Analysis.

Plasma lipids have been shown to relate to tumor biology. We aimed to analyze the effect of pre-transplant plasma lipid profiles on post-transplant tumor recurrence in patients with hepatocellular carcinoma and to identify any possible relationship between the pre-transplant lipid profile with maximum tumor diameter, number of tumor nodules, tumor differentiation, portal vein invasion, or serum biomarker levels. Patients with hepatocellular carcinoma who underwent liver transplants between 2006 and 2021 had data collected pro- spectively and were analyzed retrospectively. Patients who did not have lipid profile data before transplant and whose post-transplant follow-up period was <90 days were excluded. Patients who had pre-transplant plasma lipid data and whose post-transplant follow-up period was >90 days were included in this study (n = 254). Lower high-density lipoprotein cholesterol levels were found to be significantly associated with post-Tx recurrence (38 vs 29.5, P < .001) and were also significantly associated with macroscopic portal vein thrombosis (39 vs 30.4, P < .021). There was no significant association between plasma lipids and tumor differentiation. Higher high-density lipoprotein cholesterol levels were significantly asso- ciated with good overall and disease-free survivals (P = .024 and P = .001). Pre-transplant low plasma high-density lipoprotein cholesterol levels were significantly associated with portal vein throm- bosis and poor post-transplant overall and disease-free survivals.

Oral Supplement Containing Hydroxytyrosol and Punicalagin Improves Dyslipidemia in an Adult Population without Co-Adjuvant Treatment: A Randomized, Double-Blind, Controlled and Crossover Trial.

Hydroxytyrosol (HT) and punicalagin (PC) exert cardioprotective and antiatherosclerotic effects. This study evaluated the effect of an oral supplement containing HT and PC (SAx) on dyslipidemia in an adult population. A randomized, double-blind, controlled, crossover trial was conducted over a 20-week period. SAx significantly reduced the plasma levels of triglycerides (TG) in subjects with hypertriglyceridemia (≥150 mg/dL) (from 200.67 ± 51.38 to 155.33 ± 42.44 mg/dL; p < 0.05), while no such effects were observed in these subjects after the placebo. SAx also significantly decreased the plasma levels of low-density lipoprotein cholesterol (LDL-C) in subjects with high plasma levels of LDL-C (≥160 mg/dL) (from 179.13 ± 16.18 to 162.93 ± 27.05 mg/dL; p < 0.01), while no such positive effect was observed with the placebo. In addition, the placebo significantly reduced the plasma levels of high-density lipoprotein cholesterol (HDL-C) in the total population (from 64.49 ± 12.65 to 62.55 ± 11.57 mg/dL; p < 0.05), while SAx significantly increased the plasma levels of HDL-C in subjects with low plasma levels of HDL-C (<50 mg/dL) (from 44.25 ± 3.99 to 48.00 ± 7.27 mg/dL; p < 0.05). In conclusion, the supplement containing HT and PC exerted antiatherosclerotic and cardio-protective effects by considerably improving dyslipidemia in an adult population, without co-adjuvant treatment or adverse effects.

HDL, heart disease, and the lung

HDL, heart disease, and the lung