Plasma LDL-C Research Articles

Distribution and effect of ghrelin genotype on plasma lipid and apolipoprotein profiles in obese and nonobese Chinese subjects.

The hormone ghrelin has an important role in a wide range of metabolic and nonmetabolic processes. Ghrelin gene polymorphisms have been reported to influence obesity or lipid abnormalities in some ethnic groups. This study was conducted mainly to examine the possible association of ghrelin - 604G > A and Leu72Met polymorphisms with obesity and related traits in a Southwest Chinese population. Three hundred and eighty-six Han Chinese individuals (118 obese and 268 normal weight control subjects) in the Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Clinical and biochemical parameters were also analyzed. The genotype and allele frequencies of ghrelin gene polymorphisms in participants with obesity showed no significant difference compared to those in nonobese controls. However, in the nonobese control group, carriers of genotype Met/Met at the Leu72Met site had higher serum TC and LDL-C concentrations than those of the Leu/Leu genotype (P < 0.05). When nonobese subjects were stratified by sex, the genotype-dependent effects on TC and LDL-C were more evident, although this was observed only in females. In addition, genotype-related effects on these lipid parameters at this site were observed in male obese subjects only. The Leu72Met polymorphism of the ghrelin gene is associated with altered plasma TC and LDL-C concentrations, and the effects on TC and LDL-C levels are sex-dependent in both nonobese and obese subjects in the Chinese population of the Chengdu area.

Genetic susceptibility, dietary cholesterol intake, and plasma cholesterol levels in a Chinese population

Accompanied with nutrition transition, non-HDL-C levels of individuals in Asian countries has increased rapidly, which has caused the global epicenter of nonoptimal cholesterol to shift from Western countries to Asian countries. Thus, it is critical to underline major genetic and dietary determinants. In the current study of 2,330 Chinese individuals, genetic risk scores (GRSs) were calculated for total cholesterol (TC; GRSTC, 57 SNPs), LDL-C (GRSLDL-C, 45 SNPs), and HDL-C (GRSHDL-C, 65 SNPs) based on SNPs from the Global Lipid Genetics Consortium study. Cholesterol intake was estimated by a 74-item food-frequency questionnaire. Associations of dietary cholesterol intake with plasma TC and LDL-C strengthened across quartiles of the GRSTC (effect sizes: -0.29, 0.34, 2.45, and 6.47; Pinteraction = 0.002) and GRSLDL-C (effect sizes: -1.35, 0.17, 5.45, and 6.07; Pinteraction = 0.001), respectively. Similar interactions with non-HDL-C were observed between dietary cholesterol and GRSTC (Pinteraction = 0.001) and GRSLDL-C (Pinteraction = 0.004). The adverse effects of GRSTC on TC (effect sizes across dietary cholesterol quartiles: 0.51, 0.82, 1.21, and 1.31; Pinteraction = 0.023) and GRSLDL-C on LDL-C (effect sizes across dietary cholesterol quartiles: 0.66, 0.52, 1.12, and 1.56; Pinteraction = 0.020) were more profound in those having higher cholesterol intake compared with those with lower intake. Our findings suggest significant interactions between genetic susceptibility and dietary cholesterol intake on plasma cholesterol profiles in a Chinese population.

Plasma lipid levels and risk of primary open angle glaucoma: a genetic study using Mendelian randomization

BackgroundThe causal effects of plasma lipid concentrations and the risk of primary open angle glaucoma (POAG) are still unclear. Thus, the purpose of this study was to identify, applying a two-sample Mendelian randomization (MR) analysis, whether plasma lipid concentrations are causally associated with the risk of POAG.MethodsTwo-sample MR analysis of data from a genome-wide association study (GWAS) was performed to investigate the causal role of plasma lipid levels and POAG. A total of 185 independent single-nucleotide polymorphisms (SNPs) associated with plasma lipid levels were selected as instrumental variables (IVs). The SNPs were obtained from a meta-analysis of GWAS based on 188,577 European-ancestry individuals for MR analyses. Association with POAG for the SNPs was obtained from a GWAS conducted among the United Kingdom (UK) Biobank study participants with a total of 463,010 European-ancestry individuals. Four MR methods (inverse variance weighted [IVW], weighted mode, weighted median, and MR-Egger regression) were applied to obtain the overall causal estimate for multiple, instrumental SNPs.ResultsUsing the IVW analysis method, no evidence was found to support a causal association between plasma LDL-C level and POAG risk (β = − 0.00026; 95% CI = -0.00062, 0.00011; P = 0.165) with no significant heterogeneity among SNPs. The overall causal estimate between plasma LDL-C level and POAG was consistent using the other three MR methods. Using the four MR methods, no evidence of an association between plasma HDL-C (β = 0.00023; 95% CI = -0.00015, 0.00061; P = 0.238; IVW method) or TG levels (β = − 0.00028; 95% CI = -0.00071, 0.00015; P = 0.206; IVW method) and POAG risk was found. Sensitivity analyses did not reveal any sign of directional pleiotropy.ConclusionsThe present study did not find any evidence for a causal association between plasma lipid levels and POAG risk. Further research is needed to elucidate the potential biological mechanisms to provide a reasonable interpretation for these results.

Pectin and mango pulp both reduce plasma cholesterol in pigs but have different effects on triglycerides and bile acids

The aim of this study was to investigate the mechanisms of action of pectin as an extract (from apple) and as a major part of fruit pulp (mango) on plasma lipids and bile acids (BA). Pigs were used as a model for humans, and were divided into three groups (n = 10) fed a Control, pectin extract (Pectin) or mango pulp (Mango) diet for 28 d. Plasma samples were taken at the beginning (D0) and at days 15 (D15) and 28 (D28) when digesta samples were also collected from different segments of the small intestine. At D28, compared to the Control, Pectin significantly decreased plasma total cholesterol (TC, 18.0%, P < 0.01) and LDL-C (17.2%, P < 0.05) and increased total BA (TBA; 4.1 μmol/L; P < 0.05). Mango decreased TC (9.5%, P < 0.05). Pectin significantly increased intestinal TBA (P < 0.01), decreased total neutral sterols (TNS) including cholesterol (P < 0.05), decreased fatty acid digestibility (P < 0.01) and decreased plasma triglycerides (TG, 28.5%, P < 0.01). However, Mango significantly increased plasma TG (31.1% P < 0.05) and intestinal TNS (P < 0.05). The increases in intestinal and plasma TBA with the Pectin but not Mango, suggests that the mechanism(s) by which pectin-rich components cause plasma TC, LDL-C and TG reduction differ for soluble and particulate forms. Furthermore, the prebiotic properties of both forms of pectin were shown to include changes in the BA profiles, with significant increases in the therapeutic BA, ursodesoxycholic acid (UDCA).

The relationship between maternal vitamin D deficiency and glycolipid metabolism and adverse pregnancy outcome.

ObjectiveMaternal vitamin D deficiency is associated with glucose and lipid metabolism in the mother and offspring. Meanwhile, it can also lead to adverse pregnancy outcomes. The aim of this case‐control study was to document maternal, umbilical arterial glucose and lipid metabolic levels and correlations in pregnancies with or without vitamin D deficiency, while also investigating adverse pregnancy outcomes.Design/Participants/MeasurementsA total of 425 pregnant women who received antenatal care and delivered at Wenzhou People's Hospital were enrolled. According to their serum 25‐hydroxyvitamin D [25(OH)D] level, the pregnant women were divided into the vitamin D deficiency group [25(OH)D < 20 ng/mL, 185 participants] and the control group [25(OH)D ≥ 20 ng/mL, 240 participants]. Maternal blood samples were collected at 24‐28 weeks of gestation and delivery for 75‐g oral glucose tolerance test (OGTT), and measurements of glucose and lipid metabolite levels and 25(OH)D levels. Umbilical arterial samples were collected during delivery (33.57‐41.43 gestational weeks).ResultsCompared with control participants, vitamin D deficiency women had significantly higher concentrations of fasting blood‐glucose (P < .01), 1‐h OGTT plasma glucose (P < .01), 2‐h OGTT plasma glucose (P < .01), insulin (P < .01), HOMA‐IR (P < .01), LDL (P < .01) and triglycerides (P = .02) and lower concentrations of HOMA‐S (P < .01). Compared with the control group, vitamin D deficiency women had higher concentrations of triglycerides (P < .01) and lower concentrations of HDL‐C (P < .01) and HOMA‐β (P = .01) in infant umbilical arterial blood. Pearson's correlation analysis demonstrated that the maternal 25(OH)D level was negatively correlated with maternal plasma glucose, insulin, LDL‐C, cholesterol, triglyceride and HOMA‐IR (r = −.38, −.27, −.2, −.11, −.11, −.33 and .11; P < .01, <.01, <.01, <.05, <.05 and <.01, respectively), while there was a positive correlation between maternal serum 25(OH)D and HOMA‐S (r = .11, P < .05). The triglyceride level in the umbilical artery was negatively correlated with maternal serum 25(OH)D concentration (r = −.286, P < .01), while the HDL‐C and HOMA‐β in umbilical artery were positively related (r = .154, .103, P < .01). Compared with the control group, the incidences of pre‐eclampsia [4.8% (9/185) vs 1.25% (3/240), P = .03], gestational diabetes mellitus [19.45% (36/185) vs 12.08% (29/240), P = .04] and premature rupture of membranes [15.68% (29/185) vs 5.42% (13/240), P < .01] were higher in the vitamin D deficiency group.ConclusionVitamin D deficiency during pregnancy is associated with maternal glucose and lipid metabolism and pregnancy outcomes. Therefore, it is worth recommending to maintain vitamin D status at an optimal level in pregnant women to prevent metabolic disorders and pregnancy complications.

Assessment of pediatric hypercholesterolemia with a clinical data warehouse

Abstract Introduction Familial hypercholesterolemia (FH) in children and adolescents is a genetic cause of premature coronary heart disease. Early detection of patients with FH could improve their management and life expectancy. Methods A retrospective observational study was conducted using our university hospital clinical data warehouse including children born after 01/01/2000, with at least one available lipid profile. Phenotypic diagnosis of hypercholesterolemia was defined by a plasma LDL-C level ≥5 mmol/L (190 mg/dL). Above-threshold children were compared with below-threshold children on available features: age, sex, weight and height, plasma total, HDL, LDL cholesterol, triglycerides, creatinine, urea, protein, albumin, thyroid stimulating hormone and cortisol levels. Results 1,362 children were included, of whom 48 had at least one LDL-C measurement ≥5 mmol/L and 1,314 below (control). Only 2 children presented with a specific E78 hypercholesterolemia code versus 8 in the control group. Patients above the threshold were 1.5 years younger, with a mean cortisolaemia lower compared to the controls. Discussion Lipid profile is not routinely prescribed for children, and they are not routinely managed for their increased cholesterol levels. Lipid profile for children and adolescents were mainly prescribed in intensive care settings or in association with endocrine checkup. Hospital clinical data warehouse is an opportunity to specify practices in screening for Familial Hypercholesterolemia and lipid profile prescription in children. Key messages Lipid profile is not routinely prescribed for children. Hospital clinical data warehouse is an opportunity to specify practices in screening for Familial Hypercholesterolemia.

Chronic consumption of thermally processed palm oil or canola oil modified gut microflora of rats

Dietary oils have critical influences on human health, and thermally cooking or frying modify the components and nutritional functions of oils. Palm oil was the most widely used oil in food processing industry, but its health effects remain debatable. In the current study, we aimed to compare the effects of thermally oxidized palm oil and canola oil on gut microbiota. Palm oil or canola oil were heated at 180 °C for 10 h to prepare high-fat diets. Rats were fed high-fat diets for 3 months, and hematological properties, gut microflora composition and intestinal gene expression were examined. The results indicated that heated canola oil consumption elevated plasma total cholesterol and LDL-c levels compared with unheated canola oil, but heated palm oil do not had these effects; and consumption of heated palm oil significantly elevated the relative abundance of Lactobacillucs and Roseburia in gut, compared with non-heated palm oil or two canola oil groups. Moreover, intestinal expression of IL-22 was increased in heated palm oil fed animal, though ZO-1 and GPR41 were reduced. In conclusion, heating process may enhance the effects of palm oil on proliferation of probiotics Lactobacillucs, and weaken the effects of canola oil on cholesterol transport and metabolism.

Association Between PSD95 Gene 3'UTR Single Nucleotide Polymorphism and Risk of Acute Ischemic Stroke in Chinese Han Population.

To study the association between the 3'UTR single nucleotide polymorphism of PSD95 gene and the risk of acute ischemic stroke (AIS) in Chinese Han population. PSD95 gene 3'UTR rs191350575, rs314254, rs58197058, rs314253, rs314252, rs188777, rs11652753, rs79715480, and rs13331 genotypes of a total of 280 AIS patients and 280 healthy controls were analyzed. The prognosis outcomes of all AIS patients were analyzed after 3years of follow-up. The risk of AIS in the rs58197058 locus A allele was 1.76 times higher than the G allele (95%CI 1.53-1.92, p < 0.01). The rs314252 locus A allele carrier was 1.29 times more likely to develop AIS than the G allele (95%CI 1.14-1.45, p < 0.01). The rs13331 locus A allele was a high-risk factor for ASI (adjusted OR = 1.18, 95%CI 1.05-1.33, p = 0.01). The interaction model between Alcohol, DM, Hypertension, rs58197058, and rs314252 predicted the highest accuracy of AIS, with a corresponding sensitivity of 75.36%, specificity of 85.00%, and cross-validation consistency (CVC) of 10/10 (p < 0.01). There was a significant correlation between rs58197058, rs314252, and rs13331 SNPs and plasma FG, TC, HDL-c, and LDL-c levels in AIS patients. The PSD95 gene 3'UTR rs58197058, rs314252, and rs13331 SNPs are associated with the occurrence and prognosis of Chinese Han AIS patients.

SUN-019 Androgens Modulate Lipid Metabolism and Absorption in Control and Polycystic Ovary-Metabolic Syndrome Conditions

Introduction: In polycystic ovary syndrome (PCOS) a high plasma level of androgens has been correlated with an adverse plasma lipid profile. At present we do not know the physiological or mechanistic pathways of how androgens regulate lipid metabolism under control or PCOS conditions. We have shown flutamide, an androgen receptor (AR) inhibitor, reduces the plasma concentration of triglycerides (TG) and apoB-lipoproteins, and intestinal secretion of TG. Aim: The aim of this study was to determine the direct physiological and mechanistic effects of androgens, Testosterone (T) and dihydrotestosterone (DHT), on lipid metabolism using a PCOS-prone rodent model. Methods: Control and PCOS-prone animals were administered vehicle, T or DHT for 7 days. PCOS-prone animals also present with the Metabolic Syndrome (MetS). Following treatment animals underwent a mesenteric lymphatic cannulation procedure to determine effects on intestinal chylomicron (CM-apoB48) and lipid secretion, and absorption using radiolabelled [³H]-cholesterol and [14C]-palmitic acid. Results: Plasma LDL-C was increased with DHT treatment in control animals, and with both T & DHT treatment in PCOS. Intestinal absorption of TG and cholesterol were increased in T and DHT treated PCOS animals but not control animals. Whereas DHT reduced intestinal CM-apoB48 secretion in both control and PCOS groups. These effects were associated with changes in genes and protein expression in lipogenic (SREBP1a/c&2, SREBP1c, SREBP-2, ACC) and steroidogenic pathways (AR, ER and SRDA51) in the liver and intestine. Conclusion: These results demonstrate androgens modulate lipid metabolism and absorption. T and DHT differentially affect intestinal chylomicron secretion and lipid absorption in PCOS-MetS and control conditions. In conclusion, these results suggest that androgens may directly cause or exacerbate lipid and lipoprotein metabolism in conditions of hyperandrogenemia and the MetS.

Inhibition of JAK2/STAT3/SOCS3 signaling attenuates atherosclerosis in rabbit

BackgroundPrevious studies have indicated that the JAK/STAT signaling pathway is involved in modulating arterial adventitia inflammation response. In this study, we designed experiments to further investigate the effect of JAK2/STAT3/SOCS3 signaling in rabbit atherosclerosis process.MethodsAtherosclerosis was induced in the abdominal arteries of rabbits by balloon injury of the aorta supplemented by the atherogenic diet. Simultaneously, in the process of atherosclerosis, animals underwent either ruxolitinib treatment or not for 12 weeks. At the end of the experimental period, all rabbits were sacrificed. The plaque areas in abdominal artery, the lipid burden of plaque and the calcium burden of plaque were detected by H&E staining, Oil Red O staining and Alizarin Red staining, respectively. In addition, rabbit plasma lipids and inflammatory cytokines were measured by biochemical test kits or ELISA kits. Finally, the expression and phosphorylation levels of JAK2/STAT3/SOCS3 pathway-related proteins were detected by RT-qPCR, western blot and immunohistochemistry assays.ResultsH&E staining and CT scan analysis showed that rabbit atherosclerosis model was constructed successfully. Ruxolitinib, an inhibitor of the Janus kinase 2 (JAK2), substantially reduced the area of atherosclerotic plaques in rabbits treated with high fat diet and balloon injury of the aorta. Moreover, ruxolitinib significantly decreased IL-6, IL-1β, IFN-γ and TNF-α, but increased IL-10 and IL-17 levels in plasma of atherosclerotic rabbits. Additionally, ruxolitinib reduced plasma TC, TG and LDL-C contents and AIP value, while enhanced HDL-C level in atherosclerotic rabbits. Furthermore, we found that JAK2 and STAT3 phosphorylation were up-regulated in rabbits with atherosclerosis when compared with those of the control group, followed by the expression of SOCS3 was also increased due to the activation of JAK2 and STAT3. Interestingly, ruxolitinib could inactivate JAK2 and STAT3 pathway and decrease SOCS3 expression.ConclusionTaken together, the inhibition of JAK2/STAT3/SOCS3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.

Efficacy and Safety of Switching from Low-Dose Statin to High-Intensity Statin for Primary Prevention in Type 2 Diabetes: A Randomized Controlled Trial.

IntroductionStatin intensification is required in patients who have high-risk for cardiovascular events. However, it is unclear if this is needed in whom plasma LDL-C target was achieved with low-dose statin for primary prevention. We investigated the efficacy and safety of switching from low-dose statin to high-intensity statin among type 2 diabetes (T2D) who had achieved plasma LDL-C <100 mg/dl with low-dose statin treatment.MethodsT2D patients with no atherosclerotic cardiovascular disease who had plasma LDL-C level <100 mg/dl while taking simvastatin ≤20 mg/day were randomized to continue using the same dosage of simvastatin (low-dose statin group; LS) for 12 weeks, or to switch to atorvastatin 40 mg/day for 6 weeks, and then, if tolerated, to atorvastatin 80 mg/day for 6 weeks (high-intensity statin group; HS). Biochemical test and adverse events were evaluated at baseline, 6 weeks, and 12 weeks.ResultsOne hundred and fifty patients (76 LS, 74 HS, mean age 58.9±8.9 years, 72% female) were included. The mean baseline plasma LDL-C level on statin was slightly higher in the HS group (71.9±13.6 vs. 68.1±14.2 mg/dl, p=0.09). The HS group had a significantly lower plasma LDL-C level at both 6 and 12 weeks (both p<0.001). Plasma LDL-C <40 mg/dl was found more frequently in the HS group (23.0% vs. 3.9%, p<0.001). Discontinuation of statin due to adverse effects was more frequent in the HS group (5.4% vs. 1.3%, p=0.38 for atorvastatin 40 mg/day, 12.2% vs. 1.3%, p=0.03 for atorvastatin 80 mg/day). No serious adverse events were observed in either group.ConclusionSwitching from low-dose statins to high-intensity statins resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period.

Exercise Training Adaptations in Metabolic Syndrome Individuals on Chronic Statin Treatment.

Statins reduce atherogenic dyslipidemia and cardiovascular disease (CVD) risk in metabolic syndrome (MetS) individuals. Exercise training could also contribute to reduce CVD by improving cardiorespiratory fitness and fat oxidation. However, statin use could interfere with training adaptations. A total of 106 MetS individuals were divided into statin users (statin group, n = 46) and statin-naïve (control group, n = 60). Groups were matched by age, weight, and MetS components. Subjects completed 16 weeks of high intensity interval training (HIIT). Before and after HIIT, muscle biopsies were collected to assess mitochondrial content (citrate synthase [CS] activity) and the activity of the rate limiting β-oxidation enzyme (3-hydroxyacyl-CoA-dehydrogenase [HAD]). Fasting plasma glucose, insulin, TG, HDL-c, and LDL-c concentrations were measured. Exercise maximal fat oxidation (FOMAX) and oxygen uptake (VO2PEAK) were determined. Training improved MetS similarly in both groups (MetS z-score -0.26 ± 0.38 vs. -0.22 ± 0.31; P < 0.001 for time and P = 0.60 for time x group). Before training, the statin group had reduced muscle HAD activity and whole body FOMAX compared to the control group. However, 16 weeks of HIIT increased HAD and FOMAX in both groups (P < 0.03, time-effect). The statin group did not prevent the increases in CS with HIIT observed in the control group (38% vs 64%, respectively; P < 0.001, time-effect). Conversely, with training VO2PEAK improved less in the statin than in the control group (12% vs. 19%, respectively; P = 0.013, time × group effect). Chronic statin use in MetS does not interfere with exercise training improvements in MetS components, FOMAX, or mitochondrial muscle enzymes (ie, CS and HAD). However, the statin group attenuated the improvements in VO2PEAK with training. ClinicalTrials.gov identifier no. NCT03019796, January 13, 2017.

Cholesterol Lowering and Antioxidative Effect of Pregerminated Brown Rice in Hypercholesterolemic Rats.

Pregerminated brown rice (GBR) is assumed to be more beneficial than polished white rice (WR), with regard to nutrition and cardiovascular health. To support this with scientific evidence, cholesterol-lowering and antioxidative effects of GBR were studied in the present investigation. The most popular rice variety in Bangladesh BIRI-29 was used to prepare GBR and WR. Initially, we analyzed the proximate composition, antioxidative phytochemicals, in vitro 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging ability and anti-hemolytic effects of GBR. To examine the dietary impact and possible benefits of the GBR, experimentally-induced hypercholesterolemic (HC, 1% cholesterol) rats were fed with GBR against WR for 12 wk. At the end, plasma total cholesterol (TC), low- and high-density lipoprotein-cholesterol (LDL-C and HDL-C), triglyceride (TG), fecal TC, and hepatic TC, lipid peroxide (LPO) and proinflammatory TNFα levels were determined. Relative to WR, GBR contained higher amounts of total polyphenols, total flavonoids, β-carotene and lycopene, and exhibited a stronger in vitro DPPH-free radical scavenging ability and antihemolytic potentials. Levels of plasma TC, LDL-C, TG, and hepatic TC and TG significantly decreased, while plasma HDL-C and fecal TC levels significantly increased in the GBR-fed HC-rats, indicating dietary GBR demonstrates a stronger antilipidemic effect than WR. The hepatic levels of LPO and TNFα also decreased (p<0.05) to a greater extent in GBR-fed HC-rats than those in the WR-fed rats. It is thus concluded that dietary GBR could be a natural treatment of hypercholesterolemia and related cardiovascular risk factors, and a source of antioxidants to reduce hemolysis and related anemia.

P704Nanoliposomal anti-PCSK9 vaccine ameliorates glucose intolerance and insulin resistance in diabetic rats

Abstract Background PCSK9 inhibitors have emerged as an effective lipid-lowering approach. Although the results of available studies suggest a positive association of plasma PCSK9 levels with glycemic parameters and risk of DM, the effects of PCSK9 inhibitors on glucose intolerance and insulin resistance as the key features of DM remain unclear. Purpose The present study was directed to determine effect of vaccine-mediated PCSK9 inhibition on glucose intolerance and insulin resistance in experimental diabetic rats. Methods Nanoliposomal vaccine composing from PCSK9-linked nanoliposome particles mixed in Alum adjuvant was subcutaneously injected four times with bi-weekly intervals in Wistar-Albino rats. Two weeks after the last immunization, vaccinated and non-vaccinated rats were subjected to diabetes experiment induced by single intraperitoneal injection of streptozotocin (STZ). One week after STZ injection, glucose tolerance ability of each animal was evaluated by using oral glucose tolerance test (OGTT) on the overnight fasted rats with glucose dose at 2 g/kg. Two weeks after STZ injection, insulin tolerance test (ITT) viaintraperitoneal injection of insulin (0.8 U/kg) was performed to determine the measure of peripheral utilization of glucose. The plasma concentrations of total cholesterol (TC), LDL-C, HDL-C, and TG were measured. Results Nanoliposomal vaccine exposing PCSK9 peptide was found to provoke high-titers IgG antibody response against PCSK9 in rats, which was associated with the decrease plasma levels and function of plasma PCSK9. During the first week after STZ injection, it was indicated that the fasting blood glucose (FBG) level was 49% (−171.7±35 mg/dL, p&lt;0.0001) lower in the vaccinated diabetic (VD) rats, when compared to the diabetic control (DC) rats. OGTT assessment revealed that the VS rats had significantly improved glucose tolerance ability and recorded significant reduction in the level of blood glucose over the period of 180 min, when compared with the DC rats. Measurement of integrated areas under the glucose curve values demonstrated that blood glucose levels were significantly (p&lt;0.0001) decreased by 34.5% in the VS rats than the DC rats. In addition, ITT analysis showed that after insulin administration blood glucose level was decreased by 49.3% in the VS group compared with the DC group. The VS rats showed significantly lower (−26.65%, p=0.02) plasma LDL-C levels than the DC rats (Figure). Histopathology examination indicated that the pancreatic islet of the VS rats had a slightly decreased population of β-cells and few α-cells. Histopathology examination of the liver tissues of both VS and DC rats exhibited the normal histology with the normal hepatic architecture composed of hepatic lobules with normal central vein. Conclusions PCSK9 inhibition using liposomal vaccine can protect from glucose and insulin tolerance impairments in diabetic rats through an unknown and pancreatic-independent mechanism.

¿Existe extabilidad LDL entre dos dosis en pacientes que usan iPCSK9?

Introduction and objectives: IPCSK9 have been shown to reduce plasma LDL-C levels more than 50%. However, the stability of LDL levels in the interdose period raises questions. We analyze if the reduction of LDL-C is stable during this period.

GSK3β inhibition suppresses the hepatic lipid accumulation in Schizothorax prenanti.

Glycogen synthase kinase-3β (GSK3β) is a serine/threonine kinase involved in the regulation of embryonic development, glycogen metabolism, protein synthesis, mitosis, and apoptosis. To understand the role of GSK3β in hepatic lipid accumulation of Schizothorax prenanti, we used lithium chloride (LiCl), a GSK3β inhibitor, to inhibit the expression and activity of GSK3β. LiCl increased levels of phosphorylation of GSK3β (Ser9) and decreased the protein level of GSK3β. Plasma TG, TC, and LDL-C levels were greatly decreased after LiCl treatment. Additionally, GSK3β inhibition significantly reduced the levels of hepatic triglyceride (TG) and decreased the expression of lipogenesis-related genes in liver. Interestingly, LiCl decreased levels of phosphorylation of STAT3 (Tyr705), and then inhibited the activity of STAT3. These results indicate that in vivo LiCl treatment, which inhibited GSK3β activity, effectively decreased hepatic lipid accumulation through STAT3 in Schizothorax prenanti.

Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice

A considerable body of data from genetic and epidemiological studies strongly support a causal relationship between high lipoprotein(a) [Lp(a)] levels, and the development of atherosclerosis and cardiovascular disease. This relationship is continuous, unrelated to Lp(a) threshold, and independent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. Unfortunately, the mechanism(s) through which Lp(a) promotes atherosclerosis are not clarified yet. Suggested hypotheses include: an increased Lp(a)-associated cholesterol entrapment in the arterial intima followed by inflammatory cell recruitment, abnormal upload of proinflammatory oxidized phospholipids, impaired fibrinolysis by inhibition of plasminogen activation, and enhanced coagulation, through inhibition of the tissue factor pathway inhibitor. This review is aimed at summarizing the available evidence on the topic. There are two clinical forms, isolated hyperlipidemia(a) [HyperLp(a)] with acceptable LDL-C levels (< 70mg/dL), and combined elevation of Lp(a) and LDL-C in plasma. To date, no drugs that selectively decrease Lp(a) are available. Some novel lipid-lowering drugs can lower Lp(a) levels, but to a limited extent, as their main effect is aimed at decreasing LDL-C levels. Significant Lp(a) lowering effects were obtained with nicotinic acid at high doses. However, adverse effects apart, nicotinic acid is no longer prescribed and available in Europe for clinical use, after European Agency of Medicines (EMA) ban. The only effective therapeutic option for now is Lipoprotein Apheresis (LA), albeit with some limitations. Lastly, it is to be acknowledged that the body of evidence confirming that reducing plasma isolated elevation of Lp(a) brings cardiovascular benefit is still insufficient. However, the growing bulk of clinical, genetic, mechanistic, and epidemiological available evidence strongly suggests that Lp(a) is likely to be the smoking gun.

Cholesterol removal from human plasma with biologically modified cryogels

In this study, low molecular weight heparin immobilized P(HEMA) cryogels were fabricated for the removal of LDL-C in hypercholesterolemic human plasma. After characterization studies for P(HEMA) cryogels, effects of the parameters including medium pH, CNBr concentration, heparin concentration and contact time on heparin immobilization were investigated. Blood compatibility and cell adhesion tests were also performed, and platelet and leucocyte loss for P(HEMA)-Hp cryogels were found to be 2.95% and 4.91%, respectively. Maximum adsorption capacity for LDL-C from hypercholesterolemic human plasma was found to be 26.7 mg/g for P(HEMA)-Hp cryogel while it was only 1.67 mg/g for bare P(HEMA) cryogel. The P(HEMA)-Hp cryogels exhibit high desorption ratios up to 96% after 10 adsorption-desorption cycles with no significant decrease in the adsorption capacity. The findings indicated that these reusable P(HEMA)-based cryogels proposed good alternative adsorbents for removal of LDL-C.

Prevalence of dyslipidemia in newly diagnosed patients of type-2 diabetes mellitus at tertiary care centre of West Uttar Pradesh: A single centre study

Literature from Indian studies showed a threefold rise in the prevalence of diabetes in rural as well as urban areas and India may become the diabetic capital of the world in near future. Patients suffering from type 2 DM have more risk of developing vascular diseases because of changes in lipid profile. Diabetic dyslipidemia is more atherogenic and is characterised by increase in serum levels of total cholesterol (TC), triglycerides (TGs), or both, or decrease in serum levels of high-density lipoprotein cholesterol (HDL-C). Dyslipidemia is a risk factor for cardiovascular diseases and is modifiable. The present study was conducted to determine the prevalence of dyslipidemia in newly-diagnosed patients of type-2 diabetes mellitus. In the study, 100 newly diagnosed type 2 diabetes patients were included as cases and 100 non-diabetic subjects were included as controls. Blood samples were collected from the subjects of both the study and control groups and were analyzed for fasting and post-prandial plasma glucose, HbA1c, TC, TG, LDL-C, and HDL-C. 84% of cases had dyslipidemia whereas only 52% of controls were found to have dyslipidemia and the difference between the two groups was statistically significant (p Keywords: Type 2 diabetes mellitus, HbA1c (Glycosylated haemoglobin), Fasting blood glucose, Dyslipidemia, Triglycerides, High density lipoprotein-cholesterol.

New insights into angiopoietin-like proteins in lipid metabolism and cardiovascular disease risk.

The angiopoietin-like proteins (ANGPTLs), consisting of ANGPTL3, ANGPTL4, and ANGPTL8, have gained significant interest for their role as inhibitors of lipoprotein lipase (LPL) and for their potential as therapeutic targets for correcting dyslipidemia. This review provides an overview of the most relevant new insights on the connection between ANGPTLs, plasma lipids, and coronary artery disease. Carriers of loss-of-function variants in ANGPTL3 have a reduced risk of coronary artery disease and reduced plasma levels of triglycerides and LDL-C, while carriers of loss-of-function variants in ANGPTL4 have a reduced risk of coronary artery disease and reduced plasma levels of triglycerides and increased HDL-C. There is evidence that carrier status of ANGPTL4 loss-of-function variants may also influence risk of type 2 diabetes. ANGPTL3 is produced in liver and is released as a complex with ANGPTL8 to suppress LPL activity in fat and muscle tissue. ANGPTL4 is produced by numerous tissues and likely mainly functions as a locally released LPL inhibitor. Both proteins inactivate LPL by catalyzing the unfolding of the hydrolase domain in LPL and by promoting the cleavage of LPL. Antisense oligonucleotide and monoclonal antibody-based inactivation of ANGPTL3 reduce plasma triglyceride and LDL-C levels in human volunteers and suppress atherosclerosis in mouse models. ANGPTL3/ANGPTL8 and ANGPTL4 together assure the appropriate distribution of plasma triglycerides across tissues during different physiological conditions. Large-scale genetic studies provide strong rationale for continued research efforts to pharmacologically inactivate ANGPTL3 and possibly ANGPTL4 to reduce plasma lipids and coronary artery disease risk.